Background A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD 20  FEV 1 .
Background
A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD 20  FEV 1 .Methods We studied 170 normal subjects, 100 male and 70 female (mean ± SD age, 38 ± 8.5 and 35 ± 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD 100 Rint, EI) as well as by percent dose response ratio (DRR).
Methods
We studied 170 normal subjects, 100 male and 70 female (mean ± SD age, 38 ± 8.5 and 35 ± 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD 100 Rint, EI) as well as by percent dose response ratio (DRR).Results BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD 20 FEV 1  (r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 μmol and 1.27 μmol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV 1  in terms of reactivity (DRR).
Results
BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD 20 FEV 1  (r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 μmol and 1.27 μmol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV 1  in terms of reactivity (DRR).Conclusions Interrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed.
Conclusions
Interrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed.

Background It is known that assessment of bronchial responsiveness incorporating measurements of forced expiration can be problematic because of limited co-operation and fatigue and dizziness due to repeated forced expiratory manoeuvres. In addition, a deep inspiration, as it is required during an FEV 1  (Forced Expiratory Volume in 1 sec) procedure, causes transient bronchodilatation particularly in normals during challenge with pharmaceutical substances, resulting in interpretation difficulties [ 1 ]. Determining bronchial reactivity using a technique which measures airways resistance is less influenced by inspiratory and expiratory efforts. Furthermore, it is more sensitive to small changes in bronchoconstriction [ 2 ] and hence more suitable for studies in normal subjects, in whom the response to bronchoconstrictors is, limited [ 3 ]. The interrupter method has been shown to be a simple and non-invasive technique of measuring airway mechanics in children or patients with limited co-operation [ 4 ]. It is also suitable for diagnostic purposes in the detection and exclusion of asthma [ 5 ] and in obtaining valid rhinomanometric measurements in various groups of patients [ 6 ]. An official statement by the ATS (American Thoracic Society) on methacholine provocation indicated that the interrupter method may be useful in testing patients who cannot perform acceptable spirometry manoeuvres but its use should be restricted to laboratories with expertise in their application and interpretation [ 7 ]. Furthermore, concerns have been raised about pressure equilibration during flow interruption [ 8 ] and when small increases in resistance are used as provocation thresholds, the repeatability of the method was found unacceptably low and unsuited for clinical and research purposes [ 9 ]. In addition, the studies performed so far with this technique were done on too small numbers of subjects to allow firm scientific conclusions. We hypothesized that, since normals present with lower levels of airway obstruction during challenge, the interrupter technique in this case might be suitable and comparable with the reference PD 20 FEV 1  method, and therefore clinically useful.
Background
It is known that assessment of bronchial responsiveness incorporating measurements of forced expiration can be problematic because of limited co-operation and fatigue and dizziness due to repeated forced expiratory manoeuvres. In addition, a deep inspiration, as it is required during an FEV 1  (Forced Expiratory Volume in 1 sec) procedure, causes transient bronchodilatation particularly in normals during challenge with pharmaceutical substances, resulting in interpretation difficulties [ 1 ]. Determining bronchial reactivity using a technique which measures airways resistance is less influenced by inspiratory and expiratory efforts. Furthermore, it is more sensitive to small changes in bronchoconstriction [ 2 ] and hence more suitable for studies in normal subjects, in whom the response to bronchoconstrictors is, limited [ 3 ].The interrupter method has been shown to be a simple and non-invasive technique of measuring airway mechanics in children or patients with limited co-operation [ 4 ]. It is also suitable for diagnostic purposes in the detection and exclusion of asthma [ 5 ] and in obtaining valid rhinomanometric measurements in various groups of patients [ 6 ].An official statement by the ATS (American Thoracic Society) on methacholine provocation indicated that the interrupter method may be useful in testing patients who cannot perform acceptable spirometry manoeuvres but its use should be restricted to laboratories with expertise in their application and interpretation [ 7 ]. Furthermore, concerns have been raised about pressure equilibration during flow interruption [ 8 ] and when small increases in resistance are used as provocation thresholds, the repeatability of the method was found unacceptably low and unsuited for clinical and research purposes [ 9 ]. In addition, the studies performed so far with this technique were done on too small numbers of subjects to allow firm scientific conclusions.We hypothesized that, since normals present with lower levels of airway obstruction during challenge, the interrupter technique in this case might be suitable and comparable with the reference PD 20 FEV 1  method, and therefore clinically useful.Methods Subjects The study was conducted in a tertiary referral centre for respiratory disease and 198 subjects were initially enrolled. All subjects were healthy with a negative history and physical examination, normal blood counts, chemistries, chest radiography and spirometry. One individual from this sample reacted to the diluent control solution (0.6%), defined as a resistance difference of > 30% baseline [ 9 ] and was excluded together with non evaluable data from 27 subjects. The final data of 170 normals were finally included, consisting of 100 (59%) males and 70 (41%) females. Predicted values for spirometry were obtained according to the European Community Coal and Steel (ECCS) [ 10 ]. All participants were given detailed information of the purpose of the study, which was approved by the hospital ethics committee, and signed a consent form. They were asked to come in the next morning, avoiding all factors listed in the ATS guidelines [ 7 ] that might cause a false negative test. Methods Routine spirometry was performed according to standardized guidelines [ 11 ]. Interrupter resistance was measured at end interruption (Rint, EI) using the technique by Phagoo et al.[ 12 ], who showed that the Rint, EI reflected changes in lung mechanics more sensitively, than interrupter resistance measured at mid or begining of interruption. The Rint, EI is calculated from the airway opening pressure (time function) signal airway opening pressure Pao(t) as follows: based on the assumption that, during a brief (100 ms) airflow interruption there is equilibration between alveolar pressure (PA) and Pao, the Rint, EI is obtained by dividing the change in pressure by the immediately preceding flow. In this study we used the alternative method of opening the interrupter [ 13 ], which calculates Rint, EI from the Pao signal using a calibration resistance. The airflow interruptions were performed using the Bronchoscreen system (Jaeger, Würzburg, Germany) [ 8 ], a computerized apparatus with a combined nebulizer-shutter head, which allows the changes in resistance of the respiratory system Rint, EI) to be measured with each breath. During quiet breathing, the opening interrupter Rint, EI was calculated. The seated subject (with noseclip in place and the cheeks partly supported by a rubber mouthpiece) breathed in a relaxed manner (in order to avoid glottic artifacts) ambient air to get accustomed to the apparatus. The shutter closed within 15 ms. The time of complete airflow interruption was 100 ms. It was triggered 150 ms after the onset of expiration. The dead space of the apparatus was 0.35 L. The pressure transducer (Honeywell 142 PC 01G; Chesham, Bucks, UK) was connected via a side port directly to the mouthpiece at a distance of 18 cm from the airway opening. Rint, EI was calculated by the formula: Rint, EI = (PA/Pm) × Rref, where PA is the end interruption mouth pressure, Pm the pressure generated during free flow and Rref is a fixed serial resistance. The triggering volume was determined by integrating the signal from a low resistance Lilly Pneumotach, which had a linearity of ± 2% at a flow below 12 L/s. Before each challenge the interrupter was calibrated. A vent produced an airflow of 105 L/min, which was led through the shutter and a calibrating resistance (0.10 kPa/L/s) and the determined Rint,EI had to be within ± 10% of the reference resistance. The above method has been found valid in the presence of mild to moderate bronchoconstriction [ 14 ], conditions that are normally met during bronchial challenge. Bronchial responsiveness was measured by a rapid methacholine provocation dosimetric test, as previously described by our group with the same apparatus but using histamine instead [ 15 ]. Briefly, 1% methacholine in saline (Lofarma, Italy) was inhaled in doubling doses starting from 200 μg, until FEV 1  had fallen = 20% compared with FEV 1  after an initial saline inhalation. The bronchial aerosol provocation system (APS Jaeger, Wurzburg, Germany) was used in this procedure. The nebulizer was calibrated to draw 5 μL of solution per automatic actuation lasting 0.6 seconds. The 100 μL of aerosol bolus had a mass median aerodynamic diameter of 1.9 μm with 80% of the droplets being less than 5.5 μm at a set pressure of 1.6 bar (22.8 psi). The subjects inhaled methacholine by slow inspiratory capacity manoeuvres guided by the green colour of light emission diodes (so that inspiratory flow was <0.5l/s) and the response was assessed 1 min after each inhaled dose. Data was assessed by using two different estimates: 1) provocation dose which increases Rint, EI by 100% (PD 100 Rint, EI), calculated by interpolation from the last two points of the cumulative semilogarithmic dose-response diagram, and 2) the percent slope (dose-response ratio-DRR) of a line extending from the origin to the last point of the curve (DRR) [ 16 ]. Plateau response was defined as difference in Rint, EI <40% after the delivery of three consecutive doubling doses and/or DRR<40% after a total cumulative dose of 4 mg or a PD 100  Rint, EI >4 mg. The DRR data were analyzed from the whole sample. The 10 day reproducibility of the PD 100 Rint, EI was investigated by randomly asking 39 subjects to come again after one week for a second examination. During the second visit we compared Rint, EI with FEV 1  as measurements of response to provocation, the latter determined 30 s after the assessment of Rint, EI [ 9 , 17 ]. At least two technically correct forced expiratory manoeuvres with an FEV 1  variation within ± 5% were received and the highest value was used for calculating the dose producing a 20% fall in FEV 1  (PD 20 FEV 1 ). Statistical analysis Regression analysis and correlation, Shapiro-Wilk test for normality and the non-parametric Mann-Whitney-U-/Wilcoxon Rank Sum test with normal approximation and the x 2  test, were used for statistical analysis. The relative duplicate error was used to assess test-retest reproducibility of the PD 100 Rint, EI (assuming a normal distribution), defined as a standard deviation of the differences divided by the v2 after log transformation (approximates coefficient of variation)[ 18 ]. Agreement between PD100Rint, EI and PD 20 FEV 1  was defined and calculated according to Bland and Altman [ 19 ]. Normal bronchial responsiveness was defined at a cut-off level of > 0.8 mg methacholine [ 20 ], while negative non-response reactions were those > 2.0 mg (8.8 μmoL)[ 21 ].
Methods
Subjects The study was conducted in a tertiary referral centre for respiratory disease and 198 subjects were initially enrolled. All subjects were healthy with a negative history and physical examination, normal blood counts, chemistries, chest radiography and spirometry. One individual from this sample reacted to the diluent control solution (0.6%), defined as a resistance difference of > 30% baseline [ 9 ] and was excluded together with non evaluable data from 27 subjects. The final data of 170 normals were finally included, consisting of 100 (59%) males and 70 (41%) females. Predicted values for spirometry were obtained according to the European Community Coal and Steel (ECCS) [ 10 ]. All participants were given detailed information of the purpose of the study, which was approved by the hospital ethics committee, and signed a consent form. They were asked to come in the next morning, avoiding all factors listed in the ATS guidelines [ 7 ] that might cause a false negative test.
Subjects
The study was conducted in a tertiary referral centre for respiratory disease and 198 subjects were initially enrolled. All subjects were healthy with a negative history and physical examination, normal blood counts, chemistries, chest radiography and spirometry.One individual from this sample reacted to the diluent control solution (0.6%), defined as a resistance difference of > 30% baseline [ 9 ] and was excluded together with non evaluable data from 27 subjects. The final data of 170 normals were finally included, consisting of 100 (59%) males and 70 (41%) females. Predicted values for spirometry were obtained according to the European Community Coal and Steel (ECCS) [ 10 ]. All participants were given detailed information of the purpose of the study, which was approved by the hospital ethics committee, and signed a consent form. They were asked to come in the next morning, avoiding all factors listed in the ATS guidelines [ 7 ] that might cause a false negative test.Methods Routine spirometry was performed according to standardized guidelines [ 11 ]. Interrupter resistance was measured at end interruption (Rint, EI) using the technique by Phagoo et al.[ 12 ], who showed that the Rint, EI reflected changes in lung mechanics more sensitively, than interrupter resistance measured at mid or begining of interruption. The Rint, EI is calculated from the airway opening pressure (time function) signal airway opening pressure Pao(t) as follows: based on the assumption that, during a brief (100 ms) airflow interruption there is equilibration between alveolar pressure (PA) and Pao, the Rint, EI is obtained by dividing the change in pressure by the immediately preceding flow. In this study we used the alternative method of opening the interrupter [ 13 ], which calculates Rint, EI from the Pao signal using a calibration resistance. The airflow interruptions were performed using the Bronchoscreen system (Jaeger, Würzburg, Germany) [ 8 ], a computerized apparatus with a combined nebulizer-shutter head, which allows the changes in resistance of the respiratory system Rint, EI) to be measured with each breath. During quiet breathing, the opening interrupter Rint, EI was calculated. The seated subject (with noseclip in place and the cheeks partly supported by a rubber mouthpiece) breathed in a relaxed manner (in order to avoid glottic artifacts) ambient air to get accustomed to the apparatus. The shutter closed within 15 ms. The time of complete airflow interruption was 100 ms. It was triggered 150 ms after the onset of expiration. The dead space of the apparatus was 0.35 L. The pressure transducer (Honeywell 142 PC 01G; Chesham, Bucks, UK) was connected via a side port directly to the mouthpiece at a distance of 18 cm from the airway opening. Rint, EI was calculated by the formula: Rint, EI = (PA/Pm) × Rref, where PA is the end interruption mouth pressure, Pm the pressure generated during free flow and Rref is a fixed serial resistance. The triggering volume was determined by integrating the signal from a low resistance Lilly Pneumotach, which had a linearity of ± 2% at a flow below 12 L/s. Before each challenge the interrupter was calibrated. A vent produced an airflow of 105 L/min, which was led through the shutter and a calibrating resistance (0.10 kPa/L/s) and the determined Rint,EI had to be within ± 10% of the reference resistance. The above method has been found valid in the presence of mild to moderate bronchoconstriction [ 14 ], conditions that are normally met during bronchial challenge. Bronchial responsiveness was measured by a rapid methacholine provocation dosimetric test, as previously described by our group with the same apparatus but using histamine instead [ 15 ]. Briefly, 1% methacholine in saline (Lofarma, Italy) was inhaled in doubling doses starting from 200 μg, until FEV 1  had fallen = 20% compared with FEV 1  after an initial saline inhalation. The bronchial aerosol provocation system (APS Jaeger, Wurzburg, Germany) was used in this procedure. The nebulizer was calibrated to draw 5 μL of solution per automatic actuation lasting 0.6 seconds. The 100 μL of aerosol bolus had a mass median aerodynamic diameter of 1.9 μm with 80% of the droplets being less than 5.5 μm at a set pressure of 1.6 bar (22.8 psi). The subjects inhaled methacholine by slow inspiratory capacity manoeuvres guided by the green colour of light emission diodes (so that inspiratory flow was <0.5l/s) and the response was assessed 1 min after each inhaled dose. Data was assessed by using two different estimates: 1) provocation dose which increases Rint, EI by 100% (PD 100 Rint, EI), calculated by interpolation from the last two points of the cumulative semilogarithmic dose-response diagram, and 2) the percent slope (dose-response ratio-DRR) of a line extending from the origin to the last point of the curve (DRR) [ 16 ]. Plateau response was defined as difference in Rint, EI <40% after the delivery of three consecutive doubling doses and/or DRR<40% after a total cumulative dose of 4 mg or a PD 100  Rint, EI >4 mg. The DRR data were analyzed from the whole sample. The 10 day reproducibility of the PD 100 Rint, EI was investigated by randomly asking 39 subjects to come again after one week for a second examination. During the second visit we compared Rint, EI with FEV 1  as measurements of response to provocation, the latter determined 30 s after the assessment of Rint, EI [ 9 , 17 ]. At least two technically correct forced expiratory manoeuvres with an FEV 1  variation within ± 5% were received and the highest value was used for calculating the dose producing a 20% fall in FEV 1  (PD 20 FEV 1 ).
Methods
Routine spirometry was performed according to standardized guidelines [ 11 ]. Interrupter resistance was measured at end interruption (Rint, EI) using the technique by Phagoo et al.[ 12 ], who showed that the Rint, EI reflected changes in lung mechanics more sensitively, than interrupter resistance measured at mid or begining of interruption. The Rint, EI is calculated from the airway opening pressure (time function) signal airway opening pressure Pao(t) as follows: based on the assumption that, during a brief (100 ms) airflow interruption there is equilibration between alveolar pressure (PA) and Pao, the Rint, EI is obtained by dividing the change in pressure by the immediately preceding flow. In this study we used the alternative method of opening the interrupter [ 13 ], which calculates Rint, EI from the Pao signal using a calibration resistance.The airflow interruptions were performed using the Bronchoscreen system (Jaeger, Würzburg, Germany) [ 8 ], a computerized apparatus with a combined nebulizer-shutter head, which allows the changes in resistance of the respiratory system Rint, EI) to be measured with each breath. During quiet breathing, the opening interrupter Rint, EI was calculated. The seated subject (with noseclip in place and the cheeks partly supported by a rubber mouthpiece) breathed in a relaxed manner (in order to avoid glottic artifacts) ambient air to get accustomed to the apparatus. The shutter closed within 15 ms. The time of complete airflow interruption was 100 ms. It was triggered 150 ms after the onset of expiration. The dead space of the apparatus was 0.35 L. The pressure transducer (Honeywell 142 PC 01G; Chesham, Bucks, UK) was connected via a side port directly to the mouthpiece at a distance of 18 cm from the airway opening. Rint, EI was calculated by the formula: Rint, EI = (PA/Pm) × Rref, where PA is the end interruption mouth pressure, Pm the pressure generated during free flow and Rref is a fixed serial resistance. The triggering volume was determined by integrating the signal from a low resistance Lilly Pneumotach, which had a linearity of ± 2% at a flow below 12 L/s. Before each challenge the interrupter was calibrated. A vent produced an airflow of 105 L/min, which was led through the shutter and a calibrating resistance (0.10 kPa/L/s) and the determined Rint,EI had to be within ± 10% of the reference resistance. The above method has been found valid in the presence of mild to moderate bronchoconstriction [ 14 ], conditions that are normally met during bronchial challenge.Bronchial responsiveness was measured by a rapid methacholine provocation dosimetric test, as previously described by our group with the same apparatus but using histamine instead [ 15 ]. Briefly, 1% methacholine in saline (Lofarma, Italy) was inhaled in doubling doses starting from 200 μg, until FEV 1  had fallen = 20% compared with FEV 1  after an initial saline inhalation. The bronchial aerosol provocation system (APS Jaeger, Wurzburg, Germany) was used in this procedure. The nebulizer was calibrated to draw 5 μL of solution per automatic actuation lasting 0.6 seconds. The 100 μL of aerosol bolus had a mass median aerodynamic diameter of 1.9 μm with 80% of the droplets being less than 5.5 μm at a set pressure of 1.6 bar (22.8 psi). The subjects inhaled methacholine by slow inspiratory capacity manoeuvres guided by the green colour of light emission diodes (so that inspiratory flow was <0.5l/s) and the response was assessed 1 min after each inhaled dose.Data was assessed by using two different estimates: 1) provocation dose which increases Rint, EI by 100% (PD 100 Rint, EI), calculated by interpolation from the last two points of the cumulative semilogarithmic dose-response diagram, and 2) the percent slope (dose-response ratio-DRR) of a line extending from the origin to the last point of the curve (DRR) [ 16 ]. Plateau response was defined as difference in Rint, EI <40% after the delivery of three consecutive doubling doses and/or DRR<40% after a total cumulative dose of 4 mg or a PD 100  Rint, EI >4 mg. The DRR data were analyzed from the whole sample. The 10 day reproducibility of the PD 100 Rint, EI was investigated by randomly asking 39 subjects to come again after one week for a second examination. During the second visit we compared Rint, EI with FEV 1  as measurements of response to provocation, the latter determined 30 s after the assessment of Rint, EI [ 9 , 17 ]. At least two technically correct forced expiratory manoeuvres with an FEV 1  variation within ± 5% were received and the highest value was used for calculating the dose producing a 20% fall in FEV 1  (PD 20 FEV 1 ).Statistical analysis Regression analysis and correlation, Shapiro-Wilk test for normality and the non-parametric Mann-Whitney-U-/Wilcoxon Rank Sum test with normal approximation and the x 2  test, were used for statistical analysis. The relative duplicate error was used to assess test-retest reproducibility of the PD 100 Rint, EI (assuming a normal distribution), defined as a standard deviation of the differences divided by the v2 after log transformation (approximates coefficient of variation)[ 18 ]. Agreement between PD100Rint, EI and PD 20 FEV 1  was defined and calculated according to Bland and Altman [ 19 ]. Normal bronchial responsiveness was defined at a cut-off level of > 0.8 mg methacholine [ 20 ], while negative non-response reactions were those > 2.0 mg (8.8 μmoL)[ 21 ].
Statistical analysis
Regression analysis and correlation, Shapiro-Wilk test for normality and the non-parametric Mann-Whitney-U-/Wilcoxon Rank Sum test with normal approximation and the x 2  test, were used for statistical analysis. The relative duplicate error was used to assess test-retest reproducibility of the PD 100 Rint, EI (assuming a normal distribution), defined as a standard deviation of the differences divided by the v2 after log transformation (approximates coefficient of variation)[ 18 ]. Agreement between PD100Rint, EI and PD 20 FEV 1  was defined and calculated according to Bland and Altman [ 19 ]. Normal bronchial responsiveness was defined at a cut-off level of > 0.8 mg methacholine [ 20 ], while negative non-response reactions were those > 2.0 mg (8.8 μmoL)[ 21 ].Results Subjects' anthropometric data and baseline spirometry are shown in Table  1 . Mean values of vital capacity (VC), FEV 1  and maximal expiratory flow when 50% of the forced vital capacity (FVC) remains to be exhaled (Vmax 50 ), were higher in males by 16.3%, 14, 7% and 2.5% than in females. While Rint, EI was higher in females, possibly reflecting smaller airway size, but these differences were not statistically significant. The distribution of PD 100 Rint, EI is shown in Figure  1 . Table 1 Characteristics of the study population stratified by gender. Variables Men Women n = 100 n = 70 Age, mean (range) yr 38 (18–60) 35 (18–55) Height, mean (cm), SEM 174 (0.78) 160 (0.71) Weight, mean (kg), SEM 79 (0.9) 63 (0.9) Rint, EI, mean (kPa/l/s), SEM 0.24 (0.069) 0.29 (0.074) VCin, mean (%pred), (range) 111.5 (83–144) 95.2 (76–129) FEV 1 , mean(%pred), (range) 107.9 (75–125) 93.2 (78–110) FEV 1  % mean (range) 83 (77–92) 82 (75–90) Vmax 50 , mean (%pred), (range) 83.5 (70–155) 81 (65–145) Abbreviations : VC in: inspiratory vital capacity, FEV 1 : forced expiratory volume in 1 sec, FEV 1 %: ratio of forced expiratory volume in 1 sec to forced vital capacity, Vmax 50 : maximum flow at 50% of forced vital capacity, Rint, EI:Interrupter Resistance at End Interruption Figure 1 Analysis of the distribution of PD 100 Rint, EI (threshold dose) in males and females. Values >4 mg are derived by extrapolation. Twenty one males and ten females (18%) of our subjects exhibited bronchial hyperesponsiveness. These values were normally distributed (W = 0.93, p = 0.12), with no gender related difference (x 2  = 1.48, p = 0.22, odds = 1.79). Furthermore, 5 of these 31 subjects (3 men and 2 women, 3% of total) were found to show moderate bronchial hyperesponsiveness (PD 100 Rint, EI < 0.4 mg or < 1.66 μmol methacholine), as frequently found in current symptomatic asthmatics [ 21 ]. No correlation was found of PD 100 Rint, EI to baseline post-saline Rint, EI and the respective DRR. Subjects with negative reactions (> 8.8 μmol) showed DRRs that were ten times lesser compared to those with BHR (mean ± SD = 67.52 ± 10.66 vs 690 ± 390, p < 0.001). Plateau response was exhibited by 66 (38%) of the subjects, (36 males) without gender related statistical difference (x 2  = 0.81, p= 0.36). They had DRRs that were 2.5 times smaller compared to the subjects with normal but measurable reactions (30.1 ± 9.8 vs. 75.0 ± 49.9, p = 0.024). PD100Rint, EI was found reproducible with a duplicate error of 8.3% or 0.65 doubling doses (within 140 μg). A close correlation was found between PD 100 Rint, EI and PD 20 FEV 1  (r = 0.76, 95% CI 0.53-0.88) with relatively narrow limits of agreement (Figure  2 .) Stratification of data according to BHR status is shown in Table  2 . The interrupter method showed DRRs that were more reactive in comparison to the respective DRRs of FEV 1 (approximately seven-fold). Figure 2 Bland and Altman plot of the differences between two methods against their mean value. The limits of agreement (  -2s and   +2s) are -0.334 mg (-1.39 μmol) and 0.306 mg (1.27 μmol) respectively. The 95% confidence intervals are -0.364 to -0.303 mg and 0.275 to 0.336 mg, respectively. Table 2 Comparison of the methods described in the text in terms of threshold dose (sensitivity) and dose-response ratio (reactivity), stratified according to BHR status. NS: p value not statistically significance between the two methods. The greater reactivity of the interrupter method is shown. Methods (× ± SD) Subjects showing BHR PD 100 Rint, EI (mgs) 0.57 ± 0.20 Dose-response ratio (%/mg) 690 ± 390 PD 20 FEV 1  (mgs) 0.72 ± 0.66 Dose-response ratio (%mg) 98 ± 90 NS P < 0.05 Subjects with normal measurable reactions (> 0.8 mgs) PD 100 Rint, EI (mgs) 3.42 ± 3.10 Dose-response ratio (%/mg) 74.86 ± 49.87 PD 20 FEV 1  (mgs) 3.13 ± 2.65 Dose-response ratio (%/mg) 20 ± 3.82 NS P < 0.05 Abbreviations : BHR :Bronchial Hyperresponsiveness, Rint, EI:Interrupter Resistance at End Interruption, PD 20 FEV 1 :Dose Producing a 20% fall in FEV 1 .
Results
Subjects' anthropometric data and baseline spirometry are shown in Table  1 . Mean values of vital capacity (VC), FEV 1  and maximal expiratory flow when 50% of the forced vital capacity (FVC) remains to be exhaled (Vmax 50 ), were higher in males by 16.3%, 14, 7% and 2.5% than in females. While Rint, EI was higher in females, possibly reflecting smaller airway size, but these differences were not statistically significant. The distribution of PD 100 Rint, EI is shown in Figure  1 .Characteristics of the study population stratified by gender.VariablesMenWomenn = 100n = 70Age, mean (range) yrHeight, mean (cm), SEMWeight, mean (kg), SEMRint, EI, mean (kPa/l/s), SEMVCin, mean (%pred), (range)FEV 1 , mean(%pred), (range)FEV 1  % mean (range)Vmax 50 , mean (%pred), (range)Abbreviations : VC in: inspiratory vital capacity, FEV 1 : forced expiratory volume in 1 sec, FEV 1 %: ratio of forced expiratory volume in 1 sec to forced vital capacity, Vmax 50 : maximum flow at 50% of forced vital capacity, Rint, EI:Interrupter Resistance at End InterruptionAbbreviationsAbbreviationsTwenty one males and ten females (18%) of our subjects exhibited bronchial hyperesponsiveness. These values were normally distributed (W = 0.93, p = 0.12), with no gender related difference (x 2  = 1.48, p = 0.22, odds = 1.79). Furthermore, 5 of these 31 subjects (3 men and 2 women, 3% of total) were found to show moderate bronchial hyperesponsiveness (PD 100 Rint, EI < 0.4 mg or < 1.66 μmol methacholine), as frequently found in current symptomatic asthmatics [ 21 ]. No correlation was found of PD 100 Rint, EI to baseline post-saline Rint, EI and the respective DRR. Subjects with negative reactions (> 8.8 μmol) showed DRRs that were ten times lesser compared to those with BHR (mean ± SD = 67.52 ± 10.66 vs 690 ± 390, p < 0.001). Plateau response was exhibited by 66 (38%) of the subjects, (36 males) without gender related statistical difference (x 2  = 0.81, p= 0.36). They had DRRs that were 2.5 times smaller compared to the subjects with normal but measurable reactions (30.1 ± 9.8 vs. 75.0 ± 49.9, p = 0.024).PD100Rint, EI was found reproducible with a duplicate error of 8.3% or 0.65 doubling doses (within 140 μg). A close correlation was found between PD 100 Rint, EI and PD 20 FEV 1  (r = 0.76, 95% CI 0.53-0.88) with relatively narrow limits of agreement (Figure  2 .) Stratification of data according to BHR status is shown in Table  2 . The interrupter method showed DRRs that were more reactive in comparison to the respective DRRs of FEV 1 (approximately seven-fold).Comparison of the methods described in the text in terms of threshold dose (sensitivity) and dose-response ratio (reactivity), stratified according to BHR status. NS: p value not statistically significance between the two methods. The greater reactivity of the interrupter method is shown.Methods (× ± SD)Subjects showing BHRSubjects with normal measurable reactions (> 0.8 mgs)Abbreviations : BHR :Bronchial Hyperresponsiveness, Rint, EI:Interrupter Resistance at End Interruption, PD 20 FEV 1 :Dose Producing a 20% fall in FEV 1 .AbbreviationsAbbreviationsDiscussion In this study we have shown that the interrupter technique, and specifically PD 100 Rint, EI, is comparable to the conventional PD 20 FEV 1  method for evaluation of BHR in a large sample of normal subjects. We have also found that this technique has a specificity of 81.2% for normal subjects and its dose response ratio is 7-fold more sensitive than the conventional FEV 1  method. It is known that specific airway conductance is four times more sensitive than FEV 1  as a measure of response to provocation but the use of a body plethysmograph makes assessment of bronchial challenge expensive and time consuming. The present methodology is particularly useful in children and in the elderly, since it is non-invasive, sensitive to changes in airway calibre and requires no subject co-operation. The opening interrupter technique offers the additional advantage of simplicity and ease of application, being particularly useful in subjects unable to perform forced manoeuvres. The Rint, EI was measured during expiration above forced residual capacity (FRC), because resistance hardly changes above this level and since subjects performed relaxed tidal flow maoeuvres, measurements were not affected by variations in breathing. Furthermore, we did not correct Rint, EI by lung volumes because the variability formed in the FRC can reduce the benefit of standardization of Rint, EI and the correlation between respiratory resistance and FRC is not significant over the limited FRC range of healthy subjects [ 21 ]. Problems in repeatability have been reported when one uses provocative concentration causing a 30% increase in Rint, EI (PC 30 Rint, EI), so we assessed the PD 100 Rint, EI threshold, which is above the 95 % confidence interval at one tail direction (1.96SD) observed in our normal sample at baseline (Table  1 ). Furthermore, although a correlation of the PC 40 Rint, EI with the classical provocative concentration causing a 20% fall in FEV 1  (PC 20 FEV 1 ) has been reported (17), data on agreement are presented for the first time in this study. If a cut-off value is set at 0,4 mg PD 100 Rint, EI methacholine, which defines severe and moderate hyperresponsiveness compatible with asthma [ 22 ] then 3% of the studied normal population was found to be in this area. This is similar to the percentage found by Malo et al. [ 23 ] working with PC 20 FEV 1 as  well as to 2.5%, which represents the proportion of subjects beyond the 2 SD of the mean on one side of a normal distribution. If the PD 100 Rint, EI threshold is set at 0,8 mg methacholine [ 18 ], which includes mild BHR, then 18% of the total subjects studied had some degree of hypersensitivity. Contradictory results have been previously reported regarding the clinical significance of asymptomatic BHR. Some studies, using even stricter definitions of BHR, showed that asymptomatic BHR is of no significance [ 24 ]. In contrast other studies have reported an increased rate of decline of lung function in an asymptomatic population with BHR [ 25 ]. A plateau with a low maximal response was exhibited by 38% of the subjects, thus representing the least reactive part of the sample. Seppala et al.[ 26 ], using a method incorporating a deep inhalation (FEV 1 ) showed that 50% of normals had no calculable PC 20 FEV 1 . In this study, by direct comparison of two methods, one involving a deep inhalation, the relative effects of maximal expiratory manoeuvres on airway calibre can be indirectly assessed. The data in Table  2  show that while threshold doses between the two methods are essentially similar and not statistically significant, there is a significant difference in the DRRs between the two methods, being more pronounced in normal subjects showing BHR. Recently, Sundblad et al [ 27 ] reported a significant correlation between dose response slopes of FEV 1  and airway conductance in a large sample of subjects but not all were normals. It is known that in bronchial challenge the dose-response curve is expressed mainly by the threshold dose indicating hyperresponsiveness and the rate and magnitude of the response (hyperreactivity, DRR). The less reactive DRRs of the FEV 1  method lend support to the perturbed actomyosin equilibrium hypothesis recently described, in that with stretching there is a decrease in myosin duty cycle and the magnitude of the contractile response becomes functionally disengaged from the level of the contractile stimulus [ 28 ]. Furthemore, since there is indirect evidence of a lack of airway inflammation or remodelling that could prevent smooth muscle from stretching, our data are in agreement with those of Kolnaar et al. [ 24 ]. The fact that airway elastic recoil decreases (increase in hysteresis) when smooth muscle is contracted [ 1 ], explains the greater difference in DRRs exhibited by subjects showing BHR (the prevailing distending force of the lung allows the airway to dilate more after deep inhalation). No correlation was found in this study between BHR and baseline airway calibre, although Malo et al.[ 23 ] found a weak correlation by using a more sensitive parameter i.e. the PC 6  FEV 1 . The limits of agreement between PD 100 Rint, EI and the classical PD 20 FEV 1  were found relatively small at -1.39 μmol and 1.27 μmol respectively. This implies that this method may be used as an alternative to FEV 1  during provocation, as it is simple and easy to perform and requires no patient co-operation. Gender differences in BHR were explored because of the smaller lung size in women. Our data are in agreement with recent studies [ 29 ] that in non smoking women, lung size has no effect on bronchial sensitivity. Since RintL was found more sensitive than RintEI, a study comparing the two methods with the classical method would be interesting [ 30 ].
Discussion
In this study we have shown that the interrupter technique, and specifically PD 100 Rint, EI, is comparable to the conventional PD 20 FEV 1  method for evaluation of BHR in a large sample of normal subjects. We have also found that this technique has a specificity of 81.2% for normal subjects and its dose response ratio is 7-fold more sensitive than the conventional FEV 1  method. It is known that specific airway conductance is four times more sensitive than FEV 1  as a measure of response to provocation but the use of a body plethysmograph makes assessment of bronchial challenge expensive and time consuming. The present methodology is particularly useful in children and in the elderly, since it is non-invasive, sensitive to changes in airway calibre and requires no subject co-operation. The opening interrupter technique offers the additional advantage of simplicity and ease of application, being particularly useful in subjects unable to perform forced manoeuvres.The Rint, EI was measured during expiration above forced residual capacity (FRC), because resistance hardly changes above this level and since subjects performed relaxed tidal flow maoeuvres, measurements were not affected by variations in breathing. Furthermore, we did not correct Rint, EI by lung volumes because the variability formed in the FRC can reduce the benefit of standardization of Rint, EI and the correlation between respiratory resistance and FRC is not significant over the limited FRC range of healthy subjects [ 21 ]. Problems in repeatability have been reported when one uses provocative concentration causing a 30% increase in Rint, EI (PC 30 Rint, EI), so we assessed the PD 100 Rint, EI threshold, which is above the 95 % confidence interval at one tail direction (1.96SD) observed in our normal sample at baseline (Table  1 ). Furthermore, although a correlation of the PC 40 Rint, EI with the classical provocative concentration causing a 20% fall in FEV 1  (PC 20 FEV 1 ) has been reported (17), data on agreement are presented for the first time in this study.If a cut-off value is set at 0,4 mg PD 100 Rint, EI methacholine, which defines severe and moderate hyperresponsiveness compatible with asthma [ 22 ] then 3% of the studied normal population was found to be in this area. This is similar to the percentage found by Malo et al. [ 23 ] working with PC 20 FEV 1 as  well as to 2.5%, which represents the proportion of subjects beyond the 2 SD of the mean on one side of a normal distribution. If the PD 100 Rint, EI threshold is set at 0,8 mg methacholine [ 18 ], which includes mild BHR, then 18% of the total subjects studied had some degree of hypersensitivity. Contradictory results have been previously reported regarding the clinical significance of asymptomatic BHR. Some studies, using even stricter definitions of BHR, showed that asymptomatic BHR is of no significance [ 24 ]. In contrast other studies have reported an increased rate of decline of lung function in an asymptomatic population with BHR [ 25 ]. A plateau with a low maximal response was exhibited by 38% of the subjects, thus representing the least reactive part of the sample. Seppala et al.[ 26 ], using a method incorporating a deep inhalation (FEV 1 ) showed that 50% of normals had no calculable PC 20 FEV 1 .In this study, by direct comparison of two methods, one involving a deep inhalation, the relative effects of maximal expiratory manoeuvres on airway calibre can be indirectly assessed. The data in Table  2  show that while threshold doses between the two methods are essentially similar and not statistically significant, there is a significant difference in the DRRs between the two methods, being more pronounced in normal subjects showing BHR.Recently, Sundblad et al [ 27 ] reported a significant correlation between dose response slopes of FEV 1  and airway conductance in a large sample of subjects but not all were normals. It is known that in bronchial challenge the dose-response curve is expressed mainly by the threshold dose indicating hyperresponsiveness and the rate and magnitude of the response (hyperreactivity, DRR). The less reactive DRRs of the FEV 1  method lend support to the perturbed actomyosin equilibrium hypothesis recently described, in that with stretching there is a decrease in myosin duty cycle and the magnitude of the contractile response becomes functionally disengaged from the level of the contractile stimulus [ 28 ]. Furthemore, since there is indirect evidence of a lack of airway inflammation or remodelling that could prevent smooth muscle from stretching, our data are in agreement with those of Kolnaar et al. [ 24 ]. The fact that airway elastic recoil decreases (increase in hysteresis) when smooth muscle is contracted [ 1 ], explains the greater difference in DRRs exhibited by subjects showing BHR (the prevailing distending force of the lung allows the airway to dilate more after deep inhalation).No correlation was found in this study between BHR and baseline airway calibre, although Malo et al.[ 23 ] found a weak correlation by using a more sensitive parameter i.e. the PC 6  FEV 1 . The limits of agreement between PD 100 Rint, EI and the classical PD 20 FEV 1  were found relatively small at -1.39 μmol and 1.27 μmol respectively. This implies that this method may be used as an alternative to FEV 1  during provocation, as it is simple and easy to perform and requires no patient co-operation.Gender differences in BHR were explored because of the smaller lung size in women. Our data are in agreement with recent studies [ 29 ] that in non smoking women, lung size has no effect on bronchial sensitivity. Since RintL was found more sensitive than RintEI, a study comparing the two methods with the classical method would be interesting [ 30 ].Conclusions In summary, the interrupter technique as an index of response to provocation has been shown to be useful to assess bronchial responsiveness in normal subjects, when maximal efforts cannot be performed. We recommend threshold doses of 100% baseline, because they show reliable agreement with the classical PD20FEV1 method.
Conclusions
In summary, the interrupter technique as an index of response to provocation has been shown to be useful to assess bronchial responsiveness in normal subjects, when maximal efforts cannot be performed. We recommend threshold doses of 100% baseline, because they show reliable agreement with the classical PD20FEV1 method.List of abbreviations ATS:American Thoracic Society, BHR:Bronchial Hyperresponsiveness, DRR:Dose Response Ratio, FEV 1: Forced Expiratory Volume in 1 sec, FVC:Forced Vital Capacity, FRC:Functional Residual Capacity, PA:Alveolar Pressure, Pao: airway opening Pressure, PC 20 FEV 1 :Provocative Concentration causing a 20% fall in FEV 1 , PC 30 Rint, EI:Provocative Concentration causing a 30% increase in Rint, EI, PD 100 Rint, EI: Provocation dose which increases Rint, EI by 100%, PD 20 FEV 1 :Provocation Dose producing a 20% fall in FEV 1 , Rint, EI:Interrupter Resistance at End Interruption, VC:Vital Capacity,
List of abbreviations
ATS:American Thoracic Society, BHR:Bronchial Hyperresponsiveness, DRR:Dose Response Ratio, FEV 1: Forced Expiratory Volume in 1 sec, FVC:Forced Vital Capacity, FRC:Functional Residual Capacity, PA:Alveolar Pressure, Pao: airway opening Pressure, PC 20 FEV 1 :Provocative Concentration causing a 20% fall in FEV 1 , PC 30 Rint, EI:Provocative Concentration causing a 30% increase in Rint, EI, PD 100 Rint, EI: Provocation dose which increases Rint, EI by 100%, PD 20 FEV 1 :Provocation Dose producing a 20% fall in FEV 1 , Rint, EI:Interrupter Resistance at End Interruption, VC:Vital Capacity,Competing interests The authors declare that they have no competing interests.
Competing interests
The authors declare that they have no competing interests.Authors' contributions PP, IK, AT, SA, DB were involved with the study conception. PP, AT, SA performed the interrupter technique and collected the data. PP did the statistical analysis. PP, AT, DB prepared the manuscript. All authors read and approved the final manuscript.
Authors' contributions
PP, IK, AT, SA, DB were involved with the study conception. PP, AT, SA performed the interrupter technique and collected the data. PP did the statistical analysis. PP, AT, DB prepared the manuscript. All authors read and approved the final manuscript.Pre-publication history The pre-publication history for this paper can be accessed here:
Pre-publication history
The pre-publication history for this paper can be accessed here:


Background The typical symptoms of coronary heart disease (CHD), chest pain and breathlessness, are well-known. They are considered quite dramatic, and can thus be fairly reliably mapped by a survey. However, people might have other clearly unpleasant symptoms impairing quality of life. The aim of this study is to evaluate the appearance of these complaints of working-aged people with self-reported CHD.
Background
The typical symptoms of coronary heart disease (CHD), chest pain and breathlessness, are well-known. They are considered quite dramatic, and can thus be fairly reliably mapped by a survey. However, people might have other clearly unpleasant symptoms impairing quality of life. The aim of this study is to evaluate the appearance of these complaints of working-aged people with self-reported CHD.Methods The study consists of a postal questionnaire of randomly selected Finns in age groups 30–34, 40–44 and 50–54, a response rate of 39% (N = 15,477). The subjects were asked whether or not a doctor had told them that they had angina pectoris or had had myocardial infarction. Four randomly selected age and sex matched controls were chosen for every patient. The occurrence of self-reported dyspnoea, chest pain during anger or other kind of emotion, palpitation and perspiration without physical exercise, irregular heartbeats, flushing, trembling of hands and voice, jerking of muscles, depression and day-time sleepiness were examined. Odds ratios (OR) with 95% confidence intervals (CI), between occurrence of symptoms and CHD with and without heart infarction, were computed by multivariate logistic regression analysis.
Methods
The study consists of a postal questionnaire of randomly selected Finns in age groups 30–34, 40–44 and 50–54, a response rate of 39% (N = 15,477). The subjects were asked whether or not a doctor had told them that they had angina pectoris or had had myocardial infarction. Four randomly selected age and sex matched controls were chosen for every patient. The occurrence of self-reported dyspnoea, chest pain during anger or other kind of emotion, palpitation and perspiration without physical exercise, irregular heartbeats, flushing, trembling of hands and voice, jerking of muscles, depression and day-time sleepiness were examined. Odds ratios (OR) with 95% confidence intervals (CI), between occurrence of symptoms and CHD with and without heart infarction, were computed by multivariate logistic regression analysis.Results The sample eventually comprised 319 CHD patients. Dyspnoea, chest pain during anger or other kind of emotion, palpitation, perspiration without physical exercise, irregular heartbeats daily or almost daily, trembling of hands and voice, and jerking of muscles occurred statistically significantly more frequently among CHD patients than among controls. The CHD patients also reported more depressive mood according to Beck's inventory scores and poorer sleep and more frequent day-time sleepiness than controls. In the multivariate logistic regression analysis chest pain during anger or other kind of emotion (ORs 4.12 and 3.61) and dyspnoea (ORs 2.33 and 3.81) were the symptoms most associated with CHD.
Results
The sample eventually comprised 319 CHD patients. Dyspnoea, chest pain during anger or other kind of emotion, palpitation, perspiration without physical exercise, irregular heartbeats daily or almost daily, trembling of hands and voice, and jerking of muscles occurred statistically significantly more frequently among CHD patients than among controls. The CHD patients also reported more depressive mood according to Beck's inventory scores and poorer sleep and more frequent day-time sleepiness than controls. In the multivariate logistic regression analysis chest pain during anger or other kind of emotion (ORs 4.12 and 3.61) and dyspnoea (ORs 2.33 and 3.81) were the symptoms most associated with CHD.Conclusions Working-aged people with self-reported coronary heart disease evince a number of symptoms limiting the quality of their every day life. This aspect should be paid attention to when evaluating functional capacity of these patients.
Conclusions
Working-aged people with self-reported coronary heart disease evince a number of symptoms limiting the quality of their every day life. This aspect should be paid attention to when evaluating functional capacity of these patients.

Background In Finland, as in most industrialised countries mortality from cardiovascular diseases has shown decreasing trends since around 1970 [ 1 , 2 ]. The Mini-Finland survey from the years 1979–80 revealed that the angina pectoris symptom (i.e. reported chest pain under physical strain) may already appear in both sexes at the age of 30, though it was not until the age of 65 that it becomes more common among men compared to women [ 3 ]. The typical symptoms of coronary heart disease (CHD), chest pain and breathlessness, are well-known. They are considered quite dramatic, and thus can be fairly reliably mapped by a survey [ 4 ]. However, coronary heart disease patients also have other complaints in respect of their health, for example fatigue and sleep problems [ 5 ]. It has also been estimated that 17% to 27% of patients with coronary artery disease have major depression and a significantly larger percentage has subsyndromal symptoms of depression [ 6 ]. The diagnosis of CHD is usually based on medical examinations or register data and not on what people by themselves experience. However, people act and use health services according to what they experience to suffer from and what they experience to limit their ability to work. Since CHD patients have many other symptoms than the traditional and well-known, it is important to know what the spectrum of symptoms and complaints among working-aged people with self-reported coronary heart disease is in relation to functional capacity.
Background
In Finland, as in most industrialised countries mortality from cardiovascular diseases has shown decreasing trends since around 1970 [ 1 , 2 ]. The Mini-Finland survey from the years 1979–80 revealed that the angina pectoris symptom (i.e. reported chest pain under physical strain) may already appear in both sexes at the age of 30, though it was not until the age of 65 that it becomes more common among men compared to women [ 3 ].The typical symptoms of coronary heart disease (CHD), chest pain and breathlessness, are well-known. They are considered quite dramatic, and thus can be fairly reliably mapped by a survey [ 4 ]. However, coronary heart disease patients also have other complaints in respect of their health, for example fatigue and sleep problems [ 5 ]. It has also been estimated that 17% to 27% of patients with coronary artery disease have major depression and a significantly larger percentage has subsyndromal symptoms of depression [ 6 ].The diagnosis of CHD is usually based on medical examinations or register data and not on what people by themselves experience. However, people act and use health services according to what they experience to suffer from and what they experience to limit their ability to work. Since CHD patients have many other symptoms than the traditional and well-known, it is important to know what the spectrum of symptoms and complaints among working-aged people with self-reported coronary heart disease is in relation to functional capacity.Methods Design The Health and Social Support study (HeSSup) is a prospective etiological follow-up study on the psychosocial health of the Finnish working-aged population. The HeSSup population consisted of a random sample of 39,563 individuals drawn from the Finnish Population Register in three age groups: 30–34, 40–44, and 50–54. The survey was carried out by postal questionnaire. Forms were returned by 15,477 individuals (approximately 5,000 in each age group), a response rate of 38.9% (37.6% in 30–34, 37.9% in 40–44, and 41.1% in 50–54). The sample was subjected to a thorough analysis of non-response [ 7 ]. The analysis was made using the official statistics of the Finnish population for the corresponding age groups in 1998 to assess whether the study population adequately represented the Finnish population. Diagnosed epilepsy and diagnosed hypertension were selected to represent chronic diseases. The major reasons for refuse were the length of the questionnaire and above all suspicion of the purpose behind the request for written consent. Less educated, divorced, widowed, unemployed and those on disability pension were least willing to participate. Differences in physical conditions between the study participants and the whole population were, however, small. It was also noted that people suffering from hypertension returned the questionnaire somewhat less readily than others. Material and methods The subjects were asked whether or not a doctor had told them that they had angina pectoris or had had myocardial infarction. The perceived state of health was determined according to Likert's five-step scale (good, quite good, fair, rather poor and poor). In order to avoid small frequencies in the analyses this was modified to a three-step scale (good, fair, poor). The appearance of dyspnoea was categorised into four degrees of difficulty according to a widely used cardiovascular survey method [ 4 ]. Persons who suffered from dyspnoea when walking uphill or upstairs comprised the group of mild symptoms. Those out of breath when walking on level ground at normal speed with other people of the same age comprised the intermediate group, those who had to stop walking on level ground due to breathlessness comprised the group of difficult dyspnoea and those who became breathless even while standing still or while washing or dressing themselves, comprised the group of extremely difficult symptoms. Participants were also asked whether or not they had experienced daily or weekly chest pain during anger or other kind of emotion, palpitation and perspiration without physical exercise, flushing, trembling of hands and voice, and jerking of muscles. Irregular heartbeats daily or weekly were asked, too. Depression was estimated by Beck's [ 8 ] depression scale ranging from 0 to 63. The normal score on this scale is below 10. In mild depression the scores are between 10 and 19 [ 9 ]. It was also asked how well and how many hours a day the participants had usually slept and how often they had felt day-time sleepiness, which when occurring daily or almost daily has been proved to be associated with depression, insomnia and breath interruptions during sleep [ 10 ]. Analyses In interpretation of results the coronary heart disease (CHD) patients were divided into two groups. The first comprised coronary patients not having had heart infarction (angina pectoris group) and the second patients having had heart infarction (infarction group). In order to have the best available comparison groups, four randomly selected age and sex matched controls for comparison were selected for every patient. Thus there were altogether 740 controls for the angina pectoris group and 536 controls for the infarction group. Stroke was ruled out in the control groups, but otherwise there were no differences between the CHD groups and their respective controls. The associations, odds ratio (OR) with 95% confidence intervals (CI), between symptoms and coronary heart disease with and without heart infarction, were computed by multivariate logistic regression analysis. The analyses were made using the SAS System for Windows, release 8.2/2000.
Methods
Design The Health and Social Support study (HeSSup) is a prospective etiological follow-up study on the psychosocial health of the Finnish working-aged population. The HeSSup population consisted of a random sample of 39,563 individuals drawn from the Finnish Population Register in three age groups: 30–34, 40–44, and 50–54. The survey was carried out by postal questionnaire. Forms were returned by 15,477 individuals (approximately 5,000 in each age group), a response rate of 38.9% (37.6% in 30–34, 37.9% in 40–44, and 41.1% in 50–54). The sample was subjected to a thorough analysis of non-response [ 7 ]. The analysis was made using the official statistics of the Finnish population for the corresponding age groups in 1998 to assess whether the study population adequately represented the Finnish population. Diagnosed epilepsy and diagnosed hypertension were selected to represent chronic diseases. The major reasons for refuse were the length of the questionnaire and above all suspicion of the purpose behind the request for written consent. Less educated, divorced, widowed, unemployed and those on disability pension were least willing to participate. Differences in physical conditions between the study participants and the whole population were, however, small. It was also noted that people suffering from hypertension returned the questionnaire somewhat less readily than others.
Design
The Health and Social Support study (HeSSup) is a prospective etiological follow-up study on the psychosocial health of the Finnish working-aged population. The HeSSup population consisted of a random sample of 39,563 individuals drawn from the Finnish Population Register in three age groups: 30–34, 40–44, and 50–54. The survey was carried out by postal questionnaire. Forms were returned by 15,477 individuals (approximately 5,000 in each age group), a response rate of 38.9% (37.6% in 30–34, 37.9% in 40–44, and 41.1% in 50–54).The sample was subjected to a thorough analysis of non-response [ 7 ]. The analysis was made using the official statistics of the Finnish population for the corresponding age groups in 1998 to assess whether the study population adequately represented the Finnish population. Diagnosed epilepsy and diagnosed hypertension were selected to represent chronic diseases. The major reasons for refuse were the length of the questionnaire and above all suspicion of the purpose behind the request for written consent. Less educated, divorced, widowed, unemployed and those on disability pension were least willing to participate. Differences in physical conditions between the study participants and the whole population were, however, small. It was also noted that people suffering from hypertension returned the questionnaire somewhat less readily than others.Material and methods The subjects were asked whether or not a doctor had told them that they had angina pectoris or had had myocardial infarction. The perceived state of health was determined according to Likert's five-step scale (good, quite good, fair, rather poor and poor). In order to avoid small frequencies in the analyses this was modified to a three-step scale (good, fair, poor). The appearance of dyspnoea was categorised into four degrees of difficulty according to a widely used cardiovascular survey method [ 4 ]. Persons who suffered from dyspnoea when walking uphill or upstairs comprised the group of mild symptoms. Those out of breath when walking on level ground at normal speed with other people of the same age comprised the intermediate group, those who had to stop walking on level ground due to breathlessness comprised the group of difficult dyspnoea and those who became breathless even while standing still or while washing or dressing themselves, comprised the group of extremely difficult symptoms. Participants were also asked whether or not they had experienced daily or weekly chest pain during anger or other kind of emotion, palpitation and perspiration without physical exercise, flushing, trembling of hands and voice, and jerking of muscles. Irregular heartbeats daily or weekly were asked, too. Depression was estimated by Beck's [ 8 ] depression scale ranging from 0 to 63. The normal score on this scale is below 10. In mild depression the scores are between 10 and 19 [ 9 ]. It was also asked how well and how many hours a day the participants had usually slept and how often they had felt day-time sleepiness, which when occurring daily or almost daily has been proved to be associated with depression, insomnia and breath interruptions during sleep [ 10 ].
Material and methods
The subjects were asked whether or not a doctor had told them that they had angina pectoris or had had myocardial infarction. The perceived state of health was determined according to Likert's five-step scale (good, quite good, fair, rather poor and poor). In order to avoid small frequencies in the analyses this was modified to a three-step scale (good, fair, poor).The appearance of dyspnoea was categorised into four degrees of difficulty according to a widely used cardiovascular survey method [ 4 ]. Persons who suffered from dyspnoea when walking uphill or upstairs comprised the group of mild symptoms. Those out of breath when walking on level ground at normal speed with other people of the same age comprised the intermediate group, those who had to stop walking on level ground due to breathlessness comprised the group of difficult dyspnoea and those who became breathless even while standing still or while washing or dressing themselves, comprised the group of extremely difficult symptoms.Participants were also asked whether or not they had experienced daily or weekly chest pain during anger or other kind of emotion, palpitation and perspiration without physical exercise, flushing, trembling of hands and voice, and jerking of muscles. Irregular heartbeats daily or weekly were asked, too. Depression was estimated by Beck's [ 8 ] depression scale ranging from 0 to 63. The normal score on this scale is below 10. In mild depression the scores are between 10 and 19 [ 9 ]. It was also asked how well and how many hours a day the participants had usually slept and how often they had felt day-time sleepiness, which when occurring daily or almost daily has been proved to be associated with depression, insomnia and breath interruptions during sleep [ 10 ].Analyses In interpretation of results the coronary heart disease (CHD) patients were divided into two groups. The first comprised coronary patients not having had heart infarction (angina pectoris group) and the second patients having had heart infarction (infarction group). In order to have the best available comparison groups, four randomly selected age and sex matched controls for comparison were selected for every patient. Thus there were altogether 740 controls for the angina pectoris group and 536 controls for the infarction group. Stroke was ruled out in the control groups, but otherwise there were no differences between the CHD groups and their respective controls. The associations, odds ratio (OR) with 95% confidence intervals (CI), between symptoms and coronary heart disease with and without heart infarction, were computed by multivariate logistic regression analysis. The analyses were made using the SAS System for Windows, release 8.2/2000.
Analyses
In interpretation of results the coronary heart disease (CHD) patients were divided into two groups. The first comprised coronary patients not having had heart infarction (angina pectoris group) and the second patients having had heart infarction (infarction group). In order to have the best available comparison groups, four randomly selected age and sex matched controls for comparison were selected for every patient. Thus there were altogether 740 controls for the angina pectoris group and 536 controls for the infarction group. Stroke was ruled out in the control groups, but otherwise there were no differences between the CHD groups and their respective controls.The associations, odds ratio (OR) with 95% confidence intervals (CI), between symptoms and coronary heart disease with and without heart infarction, were computed by multivariate logistic regression analysis. The analyses were made using the SAS System for Windows, release 8.2/2000.Results The data comprised 319 patients: 185 coronary heart disease patients who had not experienced heart infarction (55.1% were men) and 134 patients who had (78.4% were men) (Table  1 ). Most of the CHD patients were in the oldest age group, and almost 90% of those who had had a heart infarction were in the age group 50–54. In all age groups the prevalence of self-reported CHD was higher among men than among women (Table  2 ). Table 1 The coronary heart disease patients studied according to age and gender Angina pectoris group Myocardial infarction group Women Men Total Women Men Total Age group     N     N     N     %     N     N     N % 30–34     16     14     30     16     4     3     7 5 40–44     20     28     48     26     3     9     12 9 50–54     47     60    107     58     22     93    115 86 Total     83    102    185    100     29    105    134 100 Table 2 Prevalence of self-reported coronary heart disease according to age and gender     Angina pectoris     Myocardial infarction Women Men Women Men Age group % % % % 30–34 0.5 0.7 0.1 0.2 40–44 0.7 1.4 0.1 0.4 50–54 1.7 2.8 0.7 4.0 Perceived state of health State of health was perceived as good or quite good by 37.3% in the angina group and by 24.6% in the infarction group. The corresponding figures in the control groups were 76.0% and 67.4%, the differences being statistically significant (p < 0.001). State of health was perceived as poor or rather poor by 28.1% in the angina group and by 32.8% in the infarction group. Symptoms and complaints At least mild breathlessness occurred in two thirds of the angina group and three fourths of the infarction group (Table  3 ). Difficult or extremely difficult breathlessness was reported by 20.2% in the angina group and by 27.8% in the infarction group. The corresponding figures in the control groups were 1.4% and 4.0%, the differences also being statistically significant (p < 0.001). Chest pain during anger or any kind of emotion, palpitation and perspiration without physical exercise, irregular heart beats, and jerking of muscles were all both daily and weekly statistically significantly more common among CHD patients than among controls. Almost daily CHD patients reported more daytime sleepiness and trembling of hands and voice than controls. CHD patients also slept more poorly than controls, and sleeping hours ≤ 6 in a day was more common among then than among controls. CHD patients scored higher on the depression scale than the controls, the average score being 10.2 (95% CI 9.0–11.4) in the angina group and 5.8 (95% CI 5.4–6.2) in the control group. In the infarction group the average score was 9.7 (95% CI 8.4–11.0). The corresponding figure in the control group was 5.9 (95% CI 5.4–6.5). In both coronary heart disease groups at least mild depression was twice as common as among controls. Flushing was the only complaint, which was not statistically significantly more common among CHD patients than among controls. Table 3 Occurrence (%) of symptoms and complaints in coronary heart disease (CHD) patients and the control population Angina pectoris Controls Myocardial infarction Controls N = 177–185 N = 728–736 N = 129–134 N = 514–525 % % p % % p At least mild dyspnoea (Rose and Blackburn 1968) 66.5 33.2 <0.001 75.4 35.3 <0.001 Chest pain during anger or emotion   Almost daily 12.2 1.0 <0.001 16.3 0.8 <0.001   Weekly 12.8 2.5 <0.001 16.3 3.3 <0.001 Palpitation without physical exercise   Almost daily 14.1 3.4 <0.001 20.8 3.5 <0.001   Weekly 15.3 5.2 <0.001 16.9 5.4 <0.001 Perspiration without physical exercise   Almost daily 22.7 9.7 <0.001 26.0 11.0 <0.001   Weekly 18.2 10.2 0.003 16.8 8.3 0.001 Irregular heart beats   Almost daily 15.7 3.5 <0.001 24.0 3.7 <0.001   Weekly 12.4 6.1 0.004 14.0 4.4 <0.001 Depression (Beck ≥ 10) 41.6 20.4 <0.001 43.3 21.0 <0.001 Sleeping hours ≤ 6 in a day 16.8 10.3 0.015 19.4 10.1 0.003 Poor sleep usually 25.0 15.4 0.002 32.1 13.0 <0.001 Daytime sleepiness   Almost daily 33.2 11.2 <0.001 32.1 14.9 <0.001 Flushing   Almost daily 11.1 7.0 0.066 10.9 7.6 0.228   Weekly 12.8 7.1 0.014 9.3 8.0 0.624 Trembling of hands   Almost daily 13.8 2.3 <0.001 9.2 3.3 0.004   Weekly 8.3 4.7 0.053 10.7 4.0 0.003 Trembling of voice   Almost daily 3.3 1.1 0.030 5.3 1.2 0.002   Weekly 3.3 1.2 0.049 3.8 2.3 0.341 Jerking of muscles   Almost daily 13.7 2.7 <0.001 12.3 4.4 0.001   Weekly 11.5 2.7 <0.001 9.2 3.8 0.011 ORs of reported symptoms In the multivariate logistic regression analysis chest pain during anger or other kind of emotion and dyspnoea were the symptoms most associated with CHD (Table  4 ). Irregular heart beats and perspiration without physical exercise were also strongly associated with heart infarction, but not with CHD without heart infarction. On the other hand, jerking of muscles was strongly associated with CHD without heart infarction, but not with heart infarction. Table 4 Age- and sex-matched ORs with 95% CI in the multivariate logistic regression analysis for reported symptoms of coronary heart disease (CHD) without and with heart infarction. All of these symptoms were in the same model. Statistically significant associations are bolded. Angina pectoris Myocardial infarction OR (95% CI) OR (95% CI) Dyspnoea 3.81 (2.16–6.72) 2.33 (1.21–4.50) Chest pain during anger or emotion* 3.61 (1.68–7.77) 4.12 (1.72–9.84) Palpitation without physical exercise* 1.19 (0.55–2.59) 1.39 (0.57–3.39) Irregular heart beats* 1.46 (0.69–3.08) 3.12 (1.28–7.60) Perspiration without physical exercise* 1.44 (0.87–2.38) 2.19 (1.15–4.14) Flushing* 1.11 (0.62–1.97) 2.02 (0.89–4.59) Trembling of hands* 1.36 (0.58–2.93) 1.01 (0.37–2.67) Trembling of voice* 2.58 (0.85–7.87) 1.17 (0.29–4.69) Jerking of muscles* 2.44 (1.20–4.96) 1.37 (0.55–3.41) Depression (Beck ≥ 10) 1.57 (0.99–2.48) 1.01 (0.52–1.98) Poor sleep 1.30 (0.74–2.27) 1.39 (0.70–2.77) Daytime sleepiness 1.24 (0.76–2.01) 1.41 (0.78–2.56) Sleeping hours ≤ 6 in a day 1.21 (0.64–2.26) 1.08 (0.50–2.33) * almost daily or weekly
Results
The data comprised 319 patients: 185 coronary heart disease patients who had not experienced heart infarction (55.1% were men) and 134 patients who had (78.4% were men) (Table  1 ). Most of the CHD patients were in the oldest age group, and almost 90% of those who had had a heart infarction were in the age group 50–54. In all age groups the prevalence of self-reported CHD was higher among men than among women (Table  2 ).The coronary heart disease patients studied according to age and genderPrevalence of self-reported coronary heart disease according to age and genderPerceived state of health State of health was perceived as good or quite good by 37.3% in the angina group and by 24.6% in the infarction group. The corresponding figures in the control groups were 76.0% and 67.4%, the differences being statistically significant (p < 0.001). State of health was perceived as poor or rather poor by 28.1% in the angina group and by 32.8% in the infarction group.
Perceived state of health
State of health was perceived as good or quite good by 37.3% in the angina group and by 24.6% in the infarction group. The corresponding figures in the control groups were 76.0% and 67.4%, the differences being statistically significant (p < 0.001). State of health was perceived as poor or rather poor by 28.1% in the angina group and by 32.8% in the infarction group.Symptoms and complaints At least mild breathlessness occurred in two thirds of the angina group and three fourths of the infarction group (Table  3 ). Difficult or extremely difficult breathlessness was reported by 20.2% in the angina group and by 27.8% in the infarction group. The corresponding figures in the control groups were 1.4% and 4.0%, the differences also being statistically significant (p < 0.001). Chest pain during anger or any kind of emotion, palpitation and perspiration without physical exercise, irregular heart beats, and jerking of muscles were all both daily and weekly statistically significantly more common among CHD patients than among controls. Almost daily CHD patients reported more daytime sleepiness and trembling of hands and voice than controls. CHD patients also slept more poorly than controls, and sleeping hours ≤ 6 in a day was more common among then than among controls. CHD patients scored higher on the depression scale than the controls, the average score being 10.2 (95% CI 9.0–11.4) in the angina group and 5.8 (95% CI 5.4–6.2) in the control group. In the infarction group the average score was 9.7 (95% CI 8.4–11.0). The corresponding figure in the control group was 5.9 (95% CI 5.4–6.5). In both coronary heart disease groups at least mild depression was twice as common as among controls. Flushing was the only complaint, which was not statistically significantly more common among CHD patients than among controls. Table 3 Occurrence (%) of symptoms and complaints in coronary heart disease (CHD) patients and the control population Angina pectoris Controls Myocardial infarction Controls N = 177–185 N = 728–736 N = 129–134 N = 514–525 % % p % % p At least mild dyspnoea (Rose and Blackburn 1968) 66.5 33.2 <0.001 75.4 35.3 <0.001 Chest pain during anger or emotion   Almost daily 12.2 1.0 <0.001 16.3 0.8 <0.001   Weekly 12.8 2.5 <0.001 16.3 3.3 <0.001 Palpitation without physical exercise   Almost daily 14.1 3.4 <0.001 20.8 3.5 <0.001   Weekly 15.3 5.2 <0.001 16.9 5.4 <0.001 Perspiration without physical exercise   Almost daily 22.7 9.7 <0.001 26.0 11.0 <0.001   Weekly 18.2 10.2 0.003 16.8 8.3 0.001 Irregular heart beats   Almost daily 15.7 3.5 <0.001 24.0 3.7 <0.001   Weekly 12.4 6.1 0.004 14.0 4.4 <0.001 Depression (Beck ≥ 10) 41.6 20.4 <0.001 43.3 21.0 <0.001 Sleeping hours ≤ 6 in a day 16.8 10.3 0.015 19.4 10.1 0.003 Poor sleep usually 25.0 15.4 0.002 32.1 13.0 <0.001 Daytime sleepiness   Almost daily 33.2 11.2 <0.001 32.1 14.9 <0.001 Flushing   Almost daily 11.1 7.0 0.066 10.9 7.6 0.228   Weekly 12.8 7.1 0.014 9.3 8.0 0.624 Trembling of hands   Almost daily 13.8 2.3 <0.001 9.2 3.3 0.004   Weekly 8.3 4.7 0.053 10.7 4.0 0.003 Trembling of voice   Almost daily 3.3 1.1 0.030 5.3 1.2 0.002   Weekly 3.3 1.2 0.049 3.8 2.3 0.341 Jerking of muscles   Almost daily 13.7 2.7 <0.001 12.3 4.4 0.001   Weekly 11.5 2.7 <0.001 9.2 3.8 0.011
Symptoms and complaints
At least mild breathlessness occurred in two thirds of the angina group and three fourths of the infarction group (Table  3 ). Difficult or extremely difficult breathlessness was reported by 20.2% in the angina group and by 27.8% in the infarction group. The corresponding figures in the control groups were 1.4% and 4.0%, the differences also being statistically significant (p < 0.001). Chest pain during anger or any kind of emotion, palpitation and perspiration without physical exercise, irregular heart beats, and jerking of muscles were all both daily and weekly statistically significantly more common among CHD patients than among controls. Almost daily CHD patients reported more daytime sleepiness and trembling of hands and voice than controls. CHD patients also slept more poorly than controls, and sleeping hours ≤ 6 in a day was more common among then than among controls. CHD patients scored higher on the depression scale than the controls, the average score being 10.2 (95% CI 9.0–11.4) in the angina group and 5.8 (95% CI 5.4–6.2) in the control group. In the infarction group the average score was 9.7 (95% CI 8.4–11.0). The corresponding figure in the control group was 5.9 (95% CI 5.4–6.5). In both coronary heart disease groups at least mild depression was twice as common as among controls. Flushing was the only complaint, which was not statistically significantly more common among CHD patients than among controls.Occurrence (%) of symptoms and complaints in coronary heart disease (CHD) patients and the control populationORs of reported symptoms In the multivariate logistic regression analysis chest pain during anger or other kind of emotion and dyspnoea were the symptoms most associated with CHD (Table  4 ). Irregular heart beats and perspiration without physical exercise were also strongly associated with heart infarction, but not with CHD without heart infarction. On the other hand, jerking of muscles was strongly associated with CHD without heart infarction, but not with heart infarction. Table 4 Age- and sex-matched ORs with 95% CI in the multivariate logistic regression analysis for reported symptoms of coronary heart disease (CHD) without and with heart infarction. All of these symptoms were in the same model. Statistically significant associations are bolded. Angina pectoris Myocardial infarction OR (95% CI) OR (95% CI) Dyspnoea 3.81 (2.16–6.72) 2.33 (1.21–4.50) Chest pain during anger or emotion* 3.61 (1.68–7.77) 4.12 (1.72–9.84) Palpitation without physical exercise* 1.19 (0.55–2.59) 1.39 (0.57–3.39) Irregular heart beats* 1.46 (0.69–3.08) 3.12 (1.28–7.60) Perspiration without physical exercise* 1.44 (0.87–2.38) 2.19 (1.15–4.14) Flushing* 1.11 (0.62–1.97) 2.02 (0.89–4.59) Trembling of hands* 1.36 (0.58–2.93) 1.01 (0.37–2.67) Trembling of voice* 2.58 (0.85–7.87) 1.17 (0.29–4.69) Jerking of muscles* 2.44 (1.20–4.96) 1.37 (0.55–3.41) Depression (Beck ≥ 10) 1.57 (0.99–2.48) 1.01 (0.52–1.98) Poor sleep 1.30 (0.74–2.27) 1.39 (0.70–2.77) Daytime sleepiness 1.24 (0.76–2.01) 1.41 (0.78–2.56) Sleeping hours ≤ 6 in a day 1.21 (0.64–2.26) 1.08 (0.50–2.33) * almost daily or weekly
ORs of reported symptoms
In the multivariate logistic regression analysis chest pain during anger or other kind of emotion and dyspnoea were the symptoms most associated with CHD (Table  4 ). Irregular heart beats and perspiration without physical exercise were also strongly associated with heart infarction, but not with CHD without heart infarction. On the other hand, jerking of muscles was strongly associated with CHD without heart infarction, but not with heart infarction.Age- and sex-matched ORs with 95% CI in the multivariate logistic regression analysis for reported symptoms of coronary heart disease (CHD) without and with heart infarction. All of these symptoms were in the same model. Statistically significant associations are bolded.3.81 (2.16–6.72)2.33 (1.21–4.50)3.61 (1.68–7.77)4.12 (1.72–9.84)3.12 (1.28–7.60)2.19 (1.15–4.14)2.44 (1.20–4.96)* almost daily or weeklyDiscussion The principal finding in this study was that many working-aged coronary heart disease patients experience unpleasant symptoms such as dyspnoea, chest pain during anger or emotion, irregular heart beats, perspiration without physical exercise, and jerking of muscles. In addition, the frequency of most of the self-reported symptoms among the study population is higher also in respect of those symptoms, which would not be expected at least among those CHD patients whose disease is in good balance. Working-aged CHD patients may be regarded as a special group compared with the main part of CHD patients who are already by age entitled to a pension. It is likely that working-aged CHD patients have experienced the most widespread and intense exposure to risk factors, which thus has caused them this disease among the first ones within their age group. As working-aged they are wished, however, to return back to normal life and work as soon as possible. According to our study they still have a lot of symptoms concerning their every day life, which harm their recovery and rehabilitation. It is also noteworthy that many of the working aged CHD patients are still in working life. Although chest pain and dyspnoea do not prevent them to work at customer service, many of the symptoms such as trembling of hands interfere their normal jobs while appearing mostly in rest. Trembling of hands and voice are also very irritating symptoms, and they may be considered shaming. Thus they may interfere social life and reduce the quality of life. The study material may be considered representative of the Finnish working-aged population, although the response rate was only 39%. Careful non-response analysis indicated that respondents and non-respondents were comparable in respect of the most important demographic variables [ 7 ]. It is possible that CHD patients respond to the questionnaire more actively than other people. On the other hand, there are certainly those among CHD patients who neglect their disease and are not willing to respond. However, we do not know for sure whether there is an over or under estimation of the associations, but we can presume that these two factors compensate each other. Moreover, it is unlikely that the principal association studied, i.e. the association between CHD and appearance of symptoms would be a substantially different one in non-participants. The findings reflect the respondents' own conception of their symptoms. The own conception of symptoms is important, since according to findings from a 3 years' follow-up of 4,000 men, self-reported coronary heart disease predicts very strongly a new coronary event [ 11 ]. In addition, the presence of anginal symptoms may be an important independent correlate of prognosis in patients with CHD [ 12 ]. Our method to determine the existence of CHD is based on the patients' report on whether a doctor had told them that they suffered from this particular disease. Thus, we cannot know for sure the accuracy of the information reported. Nowadays, CHD is rare among young people [ 1 , 2 ]. In our data there still is some. It is possible that there is a combination of several risk factors in the background. There are validated instruments, such as the generic The Short Form 36 Health Survey [ 13 ] (SF-36), the Nottingham Health Profile [ 14 ], and the Seattle Angina Questionnaire [ 15 ], to investigate health-related quality of life. Our method to examine the subject was to ask about complaints and symptoms. Most of these questions have been successfully used in cardiovascular surveys [ 4 ] and in the Finnish Twin Cohort Study [ 16 ]. In addition, mood was estimated according the Beck's depression scale [ 8 ]. The occurrence of dyspnoea and chest pain even during anger or other kind of emotion may be considered a finding that was expected. In an American study on the care of coronary heart patients at the emergency department the most frequently reported symptom was chest pain (70% among men and 71% among women) and dyspnoea (30% men and 29% among women) [ 17 ]. The typical chest pain is also a symptom more predictive of an acute coronary attack in working-aged than in older patients [ 18 ]. It was suggested as far back as 1987 that palpitations are not an independent risk factor for increased cardiac morbidity or mortality [ 19 ]. However, according to a British study those experiencing palpitations at work and while asleep were more likely to have a cardiac cause for their palpitations [ 20 ]. Our finding was that working-aged CHD patients report palpitations more often than the control population. The high occurrence of trembling of hands and voice, and jerking of muscles may be considered an unexpected finding. Most CHD patients use beta-blocking medicines, which in addition to protecting the heart muscle also reduce the adrenergic stimulation and thus relief the symptom of trembling. Concerning depression our findings support those of previous studies. One out of four of symptomatic coronary heart disease patients have namely been found to have a probable depressive disorder, but none of them had previously been identified as suffering from depression or been treated for this reason [ 21 ]. In primary care it is of vital importance to notice symptoms of this illness, since continuing depression has been found to be associated with increased risk of mortality among CHD patients following hospital discharge [ 22 ]. It has also been verified that depression is common after coronary heart disease events such as bypass grafting, coronary angioplasty, myocardial infarction and myocardial ischaemia [ 23 ]. In our study about 40% of CHD patients had at least minor depression compared with 20% among controls. The high depression rates are probably due to our method to diagnose depression at ≥ 10 points in Beck's inventory scale. Thus we do not think there are any selection bias, since the controls were randomly selected. Furthermore, it is not probable that depressed people respond to our questionnaire more readily than people not suffering from low mood. It was also of noteworthy that daytime sleepiness was connected with coronary heart disease. A cross-sectional study of 5,419 Finnish adult men found a higher prevalence of diagnosed myocardial infarction among those who slept more than nine hours, whilst those sleeping less than six hours per night had more symptomatic coronary disease [ 24 ]. In a Swedish study concerning working-aged women poor sleep was associated with an increase in spasmodic chest pain and irregular heart beat [ 25 ], whereas in men an association between difficulties falling asleep and CHD mortality has been found [ 26 ]. From previous research we know that despite having survived a life-threatening clinical event, CHD patients appear to have continued adverse behaviours such as smoking, being obese and having frequent hangovers more than the control population [ 27 ]. The follow-up of our cohort will show in what extent the symptoms we found are indicators of increased risk of CHD among working-aged people and to what extent the symptoms are result of CHD and its care. In both cases particular attention should be paid to these aspects in primary care.
Discussion
The principal finding in this study was that many working-aged coronary heart disease patients experience unpleasant symptoms such as dyspnoea, chest pain during anger or emotion, irregular heart beats, perspiration without physical exercise, and jerking of muscles. In addition, the frequency of most of the self-reported symptoms among the study population is higher also in respect of those symptoms, which would not be expected at least among those CHD patients whose disease is in good balance. Working-aged CHD patients may be regarded as a special group compared with the main part of CHD patients who are already by age entitled to a pension. It is likely that working-aged CHD patients have experienced the most widespread and intense exposure to risk factors, which thus has caused them this disease among the first ones within their age group. As working-aged they are wished, however, to return back to normal life and work as soon as possible. According to our study they still have a lot of symptoms concerning their every day life, which harm their recovery and rehabilitation. It is also noteworthy that many of the working aged CHD patients are still in working life. Although chest pain and dyspnoea do not prevent them to work at customer service, many of the symptoms such as trembling of hands interfere their normal jobs while appearing mostly in rest. Trembling of hands and voice are also very irritating symptoms, and they may be considered shaming. Thus they may interfere social life and reduce the quality of life.The study material may be considered representative of the Finnish working-aged population, although the response rate was only 39%. Careful non-response analysis indicated that respondents and non-respondents were comparable in respect of the most important demographic variables [ 7 ]. It is possible that CHD patients respond to the questionnaire more actively than other people. On the other hand, there are certainly those among CHD patients who neglect their disease and are not willing to respond. However, we do not know for sure whether there is an over or under estimation of the associations, but we can presume that these two factors compensate each other. Moreover, it is unlikely that the principal association studied, i.e. the association between CHD and appearance of symptoms would be a substantially different one in non-participants. The findings reflect the respondents' own conception of their symptoms. The own conception of symptoms is important, since according to findings from a 3 years' follow-up of 4,000 men, self-reported coronary heart disease predicts very strongly a new coronary event [ 11 ]. In addition, the presence of anginal symptoms may be an important independent correlate of prognosis in patients with CHD [ 12 ].Our method to determine the existence of CHD is based on the patients' report on whether a doctor had told them that they suffered from this particular disease. Thus, we cannot know for sure the accuracy of the information reported. Nowadays, CHD is rare among young people [ 1 , 2 ]. In our data there still is some. It is possible that there is a combination of several risk factors in the background.There are validated instruments, such as the generic The Short Form 36 Health Survey [ 13 ] (SF-36), the Nottingham Health Profile [ 14 ], and the Seattle Angina Questionnaire [ 15 ], to investigate health-related quality of life. Our method to examine the subject was to ask about complaints and symptoms. Most of these questions have been successfully used in cardiovascular surveys [ 4 ] and in the Finnish Twin Cohort Study [ 16 ]. In addition, mood was estimated according the Beck's depression scale [ 8 ].The occurrence of dyspnoea and chest pain even during anger or other kind of emotion may be considered a finding that was expected. In an American study on the care of coronary heart patients at the emergency department the most frequently reported symptom was chest pain (70% among men and 71% among women) and dyspnoea (30% men and 29% among women) [ 17 ]. The typical chest pain is also a symptom more predictive of an acute coronary attack in working-aged than in older patients [ 18 ].It was suggested as far back as 1987 that palpitations are not an independent risk factor for increased cardiac morbidity or mortality [ 19 ]. However, according to a British study those experiencing palpitations at work and while asleep were more likely to have a cardiac cause for their palpitations [ 20 ]. Our finding was that working-aged CHD patients report palpitations more often than the control population.The high occurrence of trembling of hands and voice, and jerking of muscles may be considered an unexpected finding. Most CHD patients use beta-blocking medicines, which in addition to protecting the heart muscle also reduce the adrenergic stimulation and thus relief the symptom of trembling.Concerning depression our findings support those of previous studies. One out of four of symptomatic coronary heart disease patients have namely been found to have a probable depressive disorder, but none of them had previously been identified as suffering from depression or been treated for this reason [ 21 ]. In primary care it is of vital importance to notice symptoms of this illness, since continuing depression has been found to be associated with increased risk of mortality among CHD patients following hospital discharge [ 22 ]. It has also been verified that depression is common after coronary heart disease events such as bypass grafting, coronary angioplasty, myocardial infarction and myocardial ischaemia [ 23 ]. In our study about 40% of CHD patients had at least minor depression compared with 20% among controls. The high depression rates are probably due to our method to diagnose depression at ≥ 10 points in Beck's inventory scale. Thus we do not think there are any selection bias, since the controls were randomly selected. Furthermore, it is not probable that depressed people respond to our questionnaire more readily than people not suffering from low mood.It was also of noteworthy that daytime sleepiness was connected with coronary heart disease. A cross-sectional study of 5,419 Finnish adult men found a higher prevalence of diagnosed myocardial infarction among those who slept more than nine hours, whilst those sleeping less than six hours per night had more symptomatic coronary disease [ 24 ]. In a Swedish study concerning working-aged women poor sleep was associated with an increase in spasmodic chest pain and irregular heart beat [ 25 ], whereas in men an association between difficulties falling asleep and CHD mortality has been found [ 26 ].From previous research we know that despite having survived a life-threatening clinical event, CHD patients appear to have continued adverse behaviours such as smoking, being obese and having frequent hangovers more than the control population [ 27 ]. The follow-up of our cohort will show in what extent the symptoms we found are indicators of increased risk of CHD among working-aged people and to what extent the symptoms are result of CHD and its care. In both cases particular attention should be paid to these aspects in primary care.Conclusions According to the present findings many working-aged people with self-reported coronary heart disease perceive their state of health as poor or rather poor. They suffer from a wide range of symptoms limiting their every day life. It is noteworthy that many of these symptoms are not only irritating, but constitute a threat to health. The health related quality of life is poor among working-aged coronary heart disease patients.
Conclusions
According to the present findings many working-aged people with self-reported coronary heart disease perceive their state of health as poor or rather poor. They suffer from a wide range of symptoms limiting their every day life. It is noteworthy that many of these symptoms are not only irritating, but constitute a threat to health. The health related quality of life is poor among working-aged coronary heart disease patients.Competing interests The author(s) declare that they have no competing interests.
Competing interests
The author(s) declare that they have no competing interests.Authors' contributions MPTS drafted the manuscript; SBS participated in drafting of the manuscript; MJK participated in the design of the study and the statistical analyses; LHS participated in the statistical analyses; KJM conceived of the study, and participated in its design and co-ordination. All authors have read and approved the final manuscript.
Authors' contributions
MPTS drafted the manuscript; SBS participated in drafting of the manuscript; MJK participated in the design of the study and the statistical analyses; LHS participated in the statistical analyses; KJM conceived of the study, and participated in its design and co-ordination. All authors have read and approved the final manuscript.