BackgroundChronic low back pain (CLBP) is one of the most common complaints affecting the population worldwide including in Lebanon. Until 15 years ago, surgery was the treatment of choice. However, conservative measures are now preferred because of the large number of post-surgical complications, in addition to the many conditions where surgery cannot be performed.ObjectiveThe aim of our study is to determine the effectiveness of transformational epidural injection of ozone (TFEOI) in the management of CLBP among the Lebanese population in the Nabatieh area in comparison with patients who received transformational epidural steroid injection (TFESI).MethodsA one-year (2016-2017) retrospective study where 100 patients with CLBP were selected from two hospitals  and divided into two groups. Fifty patients were treated with Ozone injections while the other 50 were treated with steroid injections. For each patient, we recorded the type of pain, irradiation, paresthesia, and the type of injection given (steroid or Ozone). We used the patients' files and contacted them via phone calls. The results of this study were reached based on Vas Score and Mac Nab criteria which are subjective questionnaires.ResultsThe study showed that the TFESI was effective for a short duration . On the other hand, TFEOI was effective over both short and long duration .ConclusionResults from this study provide that ozone injection has high benefits in the management of CLBP in the Lebanese population. General presentationLower back pain with or without sciatic nerve involvement affects roughly 80% of the population at least once in their lifetime . AccordiChronic low back pain is an increasing problem worldwide. Many studies performed in USA and China showed that back and spine impairments were more common in women. Differences in acute presentation, management, or outcome have important medical and economic implications. A high body mass index and a lack of physical activity are both risk factors for back pain in a world where obesity and overweight have increased by 28% since the year 1980 in adults .Definition of chronic low back painChronic low back pain (LBP) is a common disorder involving the muscles, nerves, and bones of the back for more than three months. Pain can vary from a sudden sharp feeling to a dull, constant ache. Presentation differs according to the cause, so properly identifying and describing symptoms leads to more accurate diagnoses. Patients complain of a combination or a single symptom of the following: dull pain, referred pain to the buttocks, legs, and feet, and pain worsening after prolonged sitting. Pain that improves within six weeks with or without conservative treatment is considered acute while chronic pain persists for more than three months (7-12 weeks) ,5.There are no specific characteristics that confirm or ignore the diagnosis of discitis in lower back pain . More tyIn the physical exam, most of the time there are not any typical characteristics of discogenic pain. Biphasic straightening from flexion is considered by some to be an indication of a disc complaint. Pain that radiates to the toes unilaterally or bilaterally is considered characteristic of discogenic low back pain. Vanharanta has described the pain radiating from the disc due to provocation with a tuning fork pressed on the processus spinosus of the affected segment . AlthougChronic lower back pain origins may include injury, diseases, or prolonged stress on a specific part of the body . CLBP maNoninvasive imaging along with a good clinical examination  should be enough to identify or rule out underlying disease processes , neurological disorders requiring surgical intervention , and psychological distress that may amplify or prolong the pain . In patiManagement of chronic low back painDifferent ways of treatment may be used in the management of chronic lower back pain. They include conservative nonpharmacologic treatment (physiotherapy), and pharmacologic treatment , and for those with severe functional disabilities, radicular symptoms, or refractory pain, epidural therapeutic injections or even surgery may be preferred .Conservative TreatmentPatients commonly use conservative treatment options with or without consulting the physician. Nonpharmacologic conservative treatment includes exercise therapy (focusing on strengthening core muscles), behavior therapy (relaxation), and acupuncture massage . AcetamiSurgerySurgery can be considered in patients with anatomic abnormalities consistent with the distribution of pain and patients with significant functional disabilities not improving even by nonsurgical treatments. Spinal fusion is used in treating back pain caused by fractures .Epidural Therapeutic InjectionsThey include Ozone and steroids injection. Both techniques were found to have benefits for lower back pain . Ozone  that activates the molecules of diatomic oxygen in a voltaic arch . UltraviSteroids are known to have an anti-inflammatory function. Steroid infiltration relieves the peri-ganglionic inflammation by ensuring recovery of the normal ganglio-neural myelin sheath, and hence nerve function, at the disease site . During The procedure of injection of OzoneEvery patient will receive local anesthesia before the injection to avoid any pain. Then the patient lies with a pillow under his abdomen to correct lumber lordosis. This maneuver makes the lumber disc area approach to the base of the superior facet of the inferior vertebra, then the neurosurgeon uses a 15 cm long, 22 G spinal needle by directing it into the disc space at an angle of 50-60⁰ approximately. The angle can be obtained by oblique views. When the annulus is reached, the surgeon should twiddle a gritty feel of the annulus. Then the needle is pushed up to the center of the disc (nucleus pulposus) then with verifying the position with anterior, posterior, and lateral imaging. The tip of the needle should be in line with the spinous process and medial to the most medial aspect of the pedicle. The discography is done by using water-soluble contrast to confirm the needle position. When the disc is pathological, the dye spreads all along up to the canal and when the disc is normal, the dye remains in the center. Once confirmed, 5-7cc of 27-40mcg of epidural oxygen-ozone gas is injected into the disc space. The distraction of the space and whitish visualization of gas on the screen confirms the presence of gas in the disc space. The needle is removed, then a sterile dressing of the injection site should be done. The procedure lasts for approximately 20 to 30 mins and the patient is discharged home within two hours ,27.Studies on chronic low back painWomen complain of lower back pain more than men do. This is probably due to their higher responsibilities as workers in addition to spending longer duration in household work and children care . A recenOne hundred fifty-nine patients  were included and were randomly assigned to two groups. Seventy-seven patients (group A) underwent intradiscal and intraforaminal injections of a steroid and an anesthetic, and 82 patients (group B) underwent the same treatment with the addition of Ozone. An Oswestry Low Back Pain Disability Questionnaire was administered before treatment and at several intervals, the last being at a six-month follow-up. Results were compared with the X2 test. The results showed that the intraforaminal and intradiscal injections of a steroid plus Ozone are more effective at six months than injections of only a steroid in the same sites .Comparative studies between Ozone and steroidAndreula Cosma and collaborators 2003 did a randomized control trial in Italy on 600 patients with lumbar disc herniation treated with a single session of Ozone therapy. All patients presented with clinical signs of lumbar disk nerve root compression with CT and/or MRI evidence of contained disk herniation. They randomized patients into two groups of 300 each. Group A received 4 mL intradiscal and 8 mL periganglionic Ozone at 27 µg/mL concentration. Group B received Ozone in a similar concentration plus steroid (1 mL Depo-Medrol 40 mg/mL) and 0.5% marcine. The outcome was assessed using modified Mac Nab criteria. Treatment was successful in 211 (70.3%) patients with excellent in 160 and good in 75 patients (p < 0.05). They concluded that Ozone therapy is a useful treatment for lumbar disk herniation that has failed to respond to conservative management and has a significant cumulative effect .Shah et al. elaborated on a prospective study that was set up from 2006 to 2008. Patients with contained discs on MRI and failed conservative trials were included in the study. Those with cauda equina syndrome or spinal tumors or infections in addition to pregnant women were excluded. A total of 93 patients were injected with intra-discal ozone. There were 34 females and 59 males with an average age of 54±13.2 years (range 32 to 78). Fifty-one patients had two-level lesions while 24 had three-level lesions. Only 18 had single-level discs. Eleven patients had both sensorimotor deficits while six had only sensory and two had only motor deficits. The remaining patients had no neurological deficit. Eleven of these patients had previous open laminectomies done (failed back) .Greenough and Fraser's score was used to study the outcome. The results showed that the mean follow-up was 27.86±3.25 months. The preoperative Greenough and Fraser score improved from a mean of 24.33±5.94 (12 to 45) to a postoperative  mean of 68.36±6.24 (50 to 75) (p < 0.001). Twenty patients had good results while 66 had excellent results according to Greenough and Fraser's score. Four patients did not follow up. Three patients had to undergo surgery in form of microdiscectomy. nine out of 13 patients with motor deficits had significant recovery (≥grade 4 power) while only three out of 17 having sensory symptoms continued to have sensory symptoms. Five patients in this series had post-operative headaches and were treated conservatively. There were no cases of infection. This study reports the successful treatment of contained lumbar disc herniation using intradiscal Ozone. However, a comparative and controlled trial will be essential to firmly establish this modality .A study was done from June 2000 to December 2006 on the use of Ozone injection using a minimally invasive percutaneous technique for the treatment of lumbar disk herniation. The study was performed on 2,900 patients affected by lumbar disk herniation. Patients were selected on the basis of clinical, psychological, neurological, and neuro-radiological criteria. Exclusion criteria were extruded hernia and/or free disc fragments, hyperalgesia paralyzing sciatica, and progressive neurological impairment of the affected limb ,31.All patients were evaluated after one month, and those showing only partial success were scheduled for a second treatment session. The study’s results were evaluated with the modified Mac Nab classification, the visual analog scale (VAS), and the Oswestry Disability index at six and 12 months. Success rates were 75% to 80% for soft disc herniation, 70% for multiple disc herniation, and 55% for failed back surgery syndrome. None of the patients suffered early or late neurological or infectious complications. Based on these results, the researchers concluded that minimally invasive percutaneous treatment by Ozone infiltration is a valuable and competitive technique that provides excellent results at low cost and without complications .ObjectivesPrevious studies and data analysis have demonstrated a considerable risk of failure and complications in both conservative and surgical treatment of chronic lower back pain, which raises concerns about seeking other treatment modalities with higher efficacy, less complication, and less risk of failure. In this study, we aim to evaluate the effectiveness of TFEO injection as an alternative treatment modality for patients with chronic lower back pain in the Lebanese population.Primary ObjectiveThe primary objective of our study is to determine the efficacy of TFEOI injection in the management of back pain in the NABATIEH area.Secondary ObjectivesWe aimed to compare the results with the patients who received steroids injection, the results among the locations of radiculopathy, and the results among male and female patients.Study designThis is a retrospective study targeting patients with CLBP who received a TFEOI or a TFESI in Al-Najdah and Sheikh Ragheb Harb hospitals in Lebanon in the area of Nabatieh. The duration of the study was from January 2016 to January 2017 (one year). In this study, we will compare the improvement in results between Ozone or steroid injections at three-time intervals .Subjects and study populationOne hundred patient files were randomly chosen from the files present in the two specified hospitals. All patients were diagnosed with CLBP 7-12 weeks) by clinical symptoms and MRI or CT-scan images. The patients were categorized according to the type of sciatica and they were divided into two groups: 50% (50 patients) were treated by transforaminal epidural ozone injection , and 50% (50 patients) received transforaminal epidural steroids injection. In Table 2 weeks bData collectionFor each patient, information was collected from their file about their name, age, gender, paresthesia’s disk, radiculopathy, presence of numbness, results of CT or MRI, and whether they received an Ozone or steroids injection and their clinical improvement after injection at one month, three months, and six months. The VAS score for pain and Mac Nab criteria were used in the assessment of pain based on questions. Each patient received a phone call asking them about their symptoms before and after the injection of ozone and steroids.VAS ScoreVAS  for pain is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. It’s a continuous scale comprised of a horizontal (HVAS) or vertical (VVAS) line, usually, 10 cm (100mm) in length, anchored by two verbal descriptors, one for each symptom extreme, “no pain” (score of 0) and “pain as bad as it could be” or “worst imaginable pain” score of 10 . It is dMac Nab modified CriteriaMac Nab scale is used to determine the outcome assessment of patient satisfaction after ozone or steroids injection therapy . The staData statistical analysisFor data entry and analysis, we used the statistical package for social sciences for windows version 22 . Independent samples t-test was used to test statistical significance. Descriptive analysis of quantitative variables will be presented as mean, standard deviation, minimum and maximum values. In addition, the software will also comprise the frequency and percentage of each category of patients. The number of missing values will be reported for each variable if present. A two-sided P-value of 0.05 was considered to be statistically significant.Numbers of females and males who had both types of injectionsFifty-eight patients of the total patients were females, and 42 patients were males. The mean age equals 49.86±12.664 years. The total number of patients is 100 patients, and the age range is 26-72 years  to assess whether the effect of steroid injection differed significantly from Ozone injection after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference after one month where the p-value = 0.072 > 0.05 and after three months the p-value = 0.672 > 0.05 from the injection between Ozone and Steroids. However, there was a significant difference after six months of injecting (p =0.001 < 0.05) between results according to VAS score after six months of injection between female patients who had ozone injections and who had steroid injections Table .Results of VAS score before and after one, three, and six months of injection of steroids and ozone in male patientsWe evaluated the number of male patients with different VAS score before and after one, three, and six months of injection of steroids and ozone Figure .VAS Score Results Before Injection of Steroids and OzoneFigures Results After One Month of Steroids Versus Ozone InjectionFigures Results After Three Months of Steroids Versus Ozone InjectionFigures Results After Six Months of Steroids Versus Ozone InjectionFigures Results Significance for Male Patients for Both Types of Injection After One, Three, and Six MonthsWe conducted an independent samples t-test  to assess whether the effect of steroid injection differed significantly from Ozone injection after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference according to the VAS score scale after one month between the male patients who had steroids injection and the male patients who had ozone injections p= 0.321 > 0.05, and after three months for the same male patients with the type of the same injection with p-value = 0.344 > 0.05. But there is a significant difference in the results between the male patients who had steroids injection and the other males who had ozone injections with p-value = 0.042 < 0.05 after six months of injections  to assess whether the effect of steroid injection differed significantly from Ozone injection according to Mac Nab criteria after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference after one month between the results with female patients who had steroids injection in comparison with the female patients who had Ozone injection with p-value = 0.304 > 0.05, and the same after three months from the injection between Ozone and Steroids between the same female patients with the same type of injections with p-value =0.738 > 0.05, however, there was a significant difference after 6-months of injecting between the results in female patients who had ozone injections and the others females who had steroids injections with p-value =0.008 < 0.05  to assess whether the effect of Steroid injection differed significantly from Ozone injection after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference according to Mac Nab criteria after one month between the male patients who had steroids injection and the male patients who had ozone injections p= 0.688 >0.05, and after three months for the same male patients with the type of the same injection with p-value= 0.630>0.05. But there is a significant difference in the results among the male patients who had steroids injection and the other males who had ozone injection with p-value=0.002 <0.05 after six months of injection  before injection, become with the same VAS score (0-1) after one, three, and six months of ozone injection  before ozone injection, after one, three months, the results one male patient had a VAS score of (1-2), and after six months the results showed one male patient who had VAS score (2-3) Table .Table On the other side of the same table, the results showed the results for five females with L4 radiculopathy who had ozone injections. The results were two females with a VAS score (6-7), two female patients with a VAS score (7-8), and only one female patient with a VAS score (8-9) before injection. The results after one month were one female patient with a VAS score (0-1), one female patient with a VAS score (1-2), and 2 female patients with a VAS score (2-3). After three months of ozone injection. Only one female patient had a VAS score of (0-1), another female patient had a VAS score of (1-2), 2 female patients had a VAS score of (2-3), and one female patient had a VAS score of (8-9). After six months the results were one female patient had a VAS score of (0-1), 3 female patients had (2-3), and one female patient had a VAS score of (8-9).Table Table Table The total number of male patients with S1 radiculopathy who had ozone injections is 13 patients. The results showed 2 male patients with a VAS score of (5-6), five male patients had a VAS score of (6-7), five male patients with a VAS score of (7-8), and only one male patient had a VAS score of (8-9) before ozone injection. After one month the results were nine male patients had a VAS score of (0-1), three male patients had a VAS score of (1-2), and one male patient had a VAS score of (8-9). After three months the results showed four male patients with of (0- 1), eight male patients had of (1-2), and only one male patient had a VAS score of (8-9). After six months of ozone injection, the results were three male patients with a VAS score of (0-1), six male patients had a VAS score of (1-2), and three male patients had a VAS score of (2-3), and only one male patient had VAS score of (8- 9) , one female patient with a VAS score of (6-7), four female patients had (7-8), and three female patients had a VAS score of (8-9). The results after one month were eight female patients with a VAS score of (0-1), two female patients had a VAS score of (1-2), and only one female patient had a VAS score of (8-9). After three months of ozone injection the results were three female patients had a VAS score of (0-1), five female patients had a VAS score of (1-2), two female patients had (2-3) and only one female patient had a VAS score of (8-9). After six months the results were three female patients had a VAS score of (0-1), three female patients had (1-2), four female patients had a VAS score of (2-3), and only one female patient had a VAS score of (8-9) Table .The objective of our study is to assess the benefit of Ozone in comparison with Steroids in CLBP in the short and long term based on Vas score and Mac Nab criteria, both of which are subjective questionnaires. According to our study, 58% of the total number of patients were females and the other 42% were males. This difference between the two genders may be due to females having a lower threshold of perception of pain and differ in reaction to it . In addiThe objective of our study was to compare the results of injecting either Ozone or steroids as a treatment for CLBP. In the female group, there was no significant difference in the results after one and three months using VAS score  between steroids and Ozone injections. However, after six months of treatment, there was a significant difference with a p value= 0.001 in females treated with Ozone. Using Mac Nab criteria in the female group, we got the same results as in using the Vas score, i.e., no significant difference was seen after one and three months but with excellent and good results with a significant difference after six months  in those into whom Ozone was injected.The same results were observed in the male group where no significant difference was seen after one and three months using both Vas score  and Mac Nab criteria. After six months of treatment, a significant difference was observed in this group when using the VAS score  and excellent and good results with a p value=0.002 using Mac Nab criteria in the Ozone group. This difference in results between the beneficial effect of steroids and the effect of ozone in the short and long term may be due to the anti-inflammatory effect of TFESI that works on the nerve, and hence its function at the disease site . This isThe TFEOI works on localized oxygenation and analgesia. Ozone is also important to muscle relaxation and vasodilation as well as reactivation of muscle metabolism, by favoring oxidation of lactate, neutralization of acidosis, enhanced synthesis of adenosine triphosphate, Ca2+ reuptake, and edema reabsorption. Moreover, a further analgesic effect may be derived from the induction of antioxidant enzymes . This maIn a study about the efficacy of TFESI in comparison to epidural Ozone injection, Joel et al. concluded that TFESI is beneficial in the short term and was not as effective in the long term. On the other hand, Ozone was found to be very safe, cheap, and effective as a short-term and long-term solution for patients with back pain along with sciatic nerve pain . M.GalluStudy limitationsMost of the limitations in this study were due to it being a retrospective study. Most of the data were collected from medical files recorded in a subjective manner with many variables missing . We did not have the privilege to evaluate real-time imaging examinations. Instead, we examined the previously performed radiological images that were available on the computer system at both sites. We were unable to calculate the incidence of CLBP and lacked follow-up with patients. In addition, the number of new cases was not clear.Study perspectivesMore studies are needed to assess the role of Ozone in treating chronic lower back pain in patients in order to observe if any complication would occur if we increased the number of patients. More retrospective and prospective studies are needed to test whether Ozone injection is better used in the management of chronic lower back pain or if there is another drug that may be of more benefit. They should focus on the causes that drive some Lebanese neurosurgeons to go to surgery quickly when they see a patient with back pain for the first time. Is it their experience? Is it pharmaceutical companies? Is it the government policies? Or it is just related to the patient’s social status? It is important to focus on risk factors of chronic low back pain, and the role of sports and physiotherapy in improving the quality of life, and in decreasing the percentage of people suffering from this medical condition.We studied patient profiles of males and females with chronic lower back pain in the Nabatieh area who were treated with either steroids or Ozone injections. According to our study results, the percentage of excellent and good outcomes after one month was approximately the same for both types of injections. Steroids were more beneficial in the short term (1-3 months). Ozone was more beneficial in the long term (six months). Studying patients with different types of radiculopathies, we found that Ozone was better than steroids over both short and long-term durations. These results give us a good plan for the management of increasing morbidity in Lebanese patients. We hope for more studies on the matter to assess the safety of this treatment on a larger scale.


Participation restriction has detrimental effects for older adults but it is unknown how participation differs for people with chronic obstructive pulmonary disease (COPD) compared to older adults of the same age without respiratory conditions. We compared scores on the Late Life Disability Instrument (LLDI) between people with COPD (study group) and a random sample of older adults (control group).Participants with COPD (study group) were recruited from two hospitals in Ontario and age- and sex-matched with a ratio of 1:2 with participants from a random sample of community-dwelling older adults who did not report having respiratory conditions (control group). The study group completed the LLDI prior to the COVID-19 pandemic and the control group completed the LLDI at the end of the first wave of the pandemic. LLDI frequency and limitation scores were compared between groups using Wilcoxon rank-sum tests.th-75th percentile 27.0–56.0) % predicted). LLDI sores were lower for the study group compared to the control group for both the frequency  and limitation  domains. The personal subscale demonstrated the largest magnitude of difference between groups (median difference -13.4 points) and the social subscale demonstrated the smallest magnitude of difference (-5.2 points).Forty-six study group participants (mean age 74.2 (SD 5.5) years) and 92 control group participants (mean age 74.4 (SD 5.4) years) were included. Fifty-four percent of the participants were female. The majority of the study group had severe COPD (median forced expiratory volume in one second of 34.5 (25People with COPD had greater participation restrictions than a random sample of older adults without ongoing respiratory conditions. The differences seen in participation between the two groups may have been reduced due to temporal confounding from the COVID-19 pandemic. While participation is relevant to all older adults, our results suggest that it is especially important that it be assessed in those with COPD. Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition worldwide ,2 that iParticipation, as it is conceptualized in the World Health Organization’s International Classification of Functioning, Disability and Health , is invoThe prevalence of participation restriction for community-dwelling adults ≥ 50 years has been estimated to be 52% with the most affected area on the Keele Assessment of Participation being mobility outside the home . In a reCOPD may present important challenges to participation that are not seen in other chronic conditions because of its progressive symptoms such as breathlessness and cough, the nature of its episodic exacerbations, and devices employed in its management such as mobility aids and supplemental oxygen . HoweverThis was a secondary analysis of data from two studies, the first a cross-sectional study in patients with COPD (conducted from February 2018 to March 2020), and the second, baseline data from a longitudinal study of older adults conducted during the coronavirus disease 2019 (COVID-19) pandemic (May to August 2020). Ethics approval for the primary studies was obtained from the Joint West Park Healthcare Centre—Toronto Central Community Care Access Centre—Toronto Grace Health Centre Research Ethics Board (17-013WP) and the Hamilton Integrated Research Ethics Board (HiREB #3878 and #10814). All participants provided informed consent prior to data collection for the primary studies; written consent was obtained from the study group and verbal consent was obtained from the control group.We recruited study group participants during routine clinical visits at two respiratory centres in Ontario- West Park Healthcare Centre in Toronto and the Firestone Institute for Respiratory Health in Hamilton. They were recruited for a cross-sectional validation study of the primary outcome measure, the LLDI. Details of recruitment, eligibility, and data collection have been reported previously . BrieflyA random sample of older adults was identified using 2016 census data and a sampling company that provides representative samples of publically available phone numbers . These p90) for the LLDI is 7.4 points for the frequency scale and 11.6 points for the limitation scale in mobility-limited older adults . Both LLDI domain scores and all four subscale scores were significantly higher for the control group than the study group with probabilities ranging from 0.63 to 0.74 (Table 2).” Page 11 (Table 2): Median (25th-75th percentile) and probabilities added to the table.Page 12 Lines 184-188: “The largest magnitude of difference between groups was seen for the personal subscale of the frequency domain (median difference 13.4 points), followed by the management and instrumental subscales of the limitation domain , with the smallest magnitude of difference being for the social subscale of the frequency domain (median difference 5.2 points).”Page 13 Lines 207-212: We have adjusted this part of the discussion since the subscales with the largest mean difference and the largest median difference were different. 4. The fact that the study was conducted at different time frames is a major limitation. Please justify that.R: Given that this was a secondary analysis, we were unable to control when the data were collected. However, this has been included as a limitation on Pages 15-16 Lines 268-276: “And finally, the control group completed the study during the first wave of the COVID-19 pandemic at which time there were social and public health restrictions in place. This difference in social circumstances might have impacted the frequency of participation in life tasks, making the control group results non-generalizable to non-pandemic times. The frequency of social activities was low in both groups and it is likely that the control group would have shown even higher scores on this subscale had public health restrictions not been in place at the time. As such, the differences seen in the participation scores between the two groups may have been attenuated due to temporal confounding.”5. Do your sample size adequate?R: Because this was a secondary analysis, we did not calculate a sample size a priori. For the frequency domain, assuming a pooled standard deviation of 10, power of 80% and alpha of 5%, we would need 38 participants in the study group and 76 participants in the control group to detect a difference of 5 points. For the limitation domain, assuming a pooled standard deviation of 15, power of 80% and alpha of 5%, we would need 44 participants in the study group and 88 participants in the control group to detect a difference of 9 points. With 46 study group participants and 92 control group participants, we were powered to detect clinically important differences. 6. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdfR: We have made adjustments to the formatting to ensure the manuscript meets the style requirements. 7. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.R: We have corrected the financial disclosure section so that it matches the funding information. http://journals.plos.org/plosone/s/supporting-information. 8. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: We have added captions for the S1 Full Sample Analysis and S2 Data File at the end of the manuscript and referred to them in the text where appropriate.Reviewer #1: This is an interesting study that compares limitations to participation in a cohort of subjects with advanced COPD against age and sex matched control subjects. I would recommend the following revisions be undertaken:Major comments:1) One of the major limitations of this study is that it is temporally confounded. The control group completed the questionnaire during the first wave of the COVID-19 pandemic when social and public health restrictions were in place, whereas all of the people from the study group participated prior to the pandemic. Accordingly, the control groups’ frequency of participating in these life tasks was likely impacted, highlighting the extent towhich participation is restricted for older adults during a pandemic. The overall effect of this confounding would have been to reduce inter-group differences seen on the LLDI scores. I think that this major limitation has to be mentioned and explained within the abstract of the paper, and the abstract has to conclude that 'People with COPD had greater participation restrictions than a random sample of older adults without ongoing respiratory conditions, but differences in participation restriction seen in this study may have been reduced due to temporal confounding.R: As suggested, we have added to the methods section of the abstract on Page 2 Lines 31-33: “The study group completed the LLDI prior to the COVID-19 pandemic and the control group completed the LLDI during the first wave of the pandemic.” as well as to the abstract conclusion on Pages 2-3 Lines 44-45: “The differences seen in participation between the two groups may have been reduced due to temporal confounding from the COVID-19 pandemic.” 2) The authors state on page 6 that "The minimal detectable change score (MDC90) for theLLDI is 7.4 points for the frequency scale and 11.6 points for the limitation scale in mobility limited older adults." Since the between-group differences in this study were less than these MDC90 scores does this mean that the differences are not clinically significant between groups? Please clarify.R: The reviewer is correct that the MDC90 values reported in a study of mobility limited older adults were 7.4 and 11.6 points for frequency and limitation, respectively. However, it is also important to note that MDC values are population-specific. We have previously established MDC95 values in people with COPD that were lower than what was reported in the study of older adults  :138-146.). We have added reference to these values into the manuscript on Page 7 Lines 132-133: “…and the MDC95 is 4.8 points for the frequency scale and 7.2 points for the limitation scale in people with COPD [13].” We have updated the results on Pages 12 Lines 180-184 to reflect both sets of previously established MDC values: “The difference in median scores for the frequency and limitation domains for the two groups was higher than the MDC95 established in people with COPD  but lower than the MDC90 established in mobility-limited older adults for the frequency and limitation domains  .” The magnitude of differences seen in participation between the groups may have been reduced due to temporal confounding as previously mentioned. 3) Did the control group undergo lung function testing? If not, how can we be sure they did not have COPD?R: Unfortunately, we do not have pulmonary function test data for the control group participants. We have updated the manuscript to indicate that control group participants were those who did not “report having respiratory conditions” (Page 2 Lines 30-31) and that we excluded participants if they had “physician-diagnosed respiratory condition” (Page 8 Line 151). We have also added this as a limitation on Pages 15-16 Lines 267-268: “In addition, we did not have pulmonary function test results from the control group participants and it is possible that some of them had undiagnosed respiratory disease.”4) A Figure 1 flow diagram needs to be added which shows how the study subjects were recruited and included/excluded and which subjects were ultimately included in the final study analysis.R: A flow diagram  has been added to show recruitment, inclusion and exclusion. 5) I note that from the primary studies, LLDI scores were collected in 96 people with COPD and 272 older adults. For this paper, only 46 study group participants and 92 control group participants were retained. This means that a lot of interesting collected data has not been analyzed. I think it would be interesting to see the LLDI scores for the entire COPD cohort and the entire 272 control cohort. This analysis could be added to the paper, and the between-group differences could be adjusted for age and sex. This additional age and sex adjusted analysis would be complementary to the case-control analysis.R: Of the 272 participants in the general sample of older adults, there were 202 who had complete scores for the LLDI and did not have a respiratory condition. The full sample (96 study group participants and 202 control group participants) was compared using quantile regression including age and sex as covariates and having COPD was a significant predictor of both frequency of and limitations in participation. We have added to the methods on Page 8 Lines 144-146: "As a sensitivity analysis, we also compared LLDI scores between the full samples of people with and without respiratory disease, without age- and sex-matching using quantile regression with age and sex as covariates." We have also added to the results on Page 12 Lines 177-179: "These results were similar when the LLDI scores of the full sample of 96 people with COPD and 202 people without respiratory disease were compared ."6) Minor comment- please delete the dots showing outliers from figs 1 and 2- they are distracting and not needed.R: Figures 2 and 3 (previously figures 1 and 2) have been revised as requested. Reviewer #2: This is a well-written manuscript, an interesting and relevant work on participation in people with chronic obstructive pulmonary disease (COPD). The authors have compared the level of participation between people with COPD and community-dwelling older adults without lung disease. People with COPD presented with greater participation restrictions compared to their peers without chronic respiratory conditions. Please find below some major and minor concerns the authors should address before publication.Abstract, Minor1. The LLDI abbreviation should be indicated at its first appearance in the text.R: This has been added (Page 2 Line 27). Results, Minor2. In Table 1, the presentation of statistical differences between groups should be revised to support the manuscript text. Some symbols used should be moved to the first column for a description of the variables, and only statistical differences should be indicated in the middle and left data columns. It is not clear to the reader which frequencies of self-reported general health differences are between groups.R: Table 1 on Pages 9-10 has been revised to include statistical comparisons between the two groups so that column 2 presents the study group data, column 3 present the control group data and column 4 presents the between-group p-values. Results, Major3. In the study group, is there any subanalysis available on differences in LLDI Participation scores between people with COPD on Long-term home oxygen therapy (LTOT) compared to those who are not? This would bring new information to the COPD literature. The authors should also provide in Table 1 the number of study group participants on LTOT, as it could impact Participation due to the use of non-portable oxygen delivery devices.R: We have added supplemental oxygen use for the study group to Table 1 on Page 9. While the use of supplemental oxygen may impact participation frequency and limitations, we chose not to explore it in the current paper as it has been previously investigated in another secondary analysis involving this data Discussion, Minor4. Page 13, line 225: please consider the replacement of 'pathologies' for 'diseases' or 'illnesses'.R: This has been changed to “health conditions” (Page 15 Line 254).5. Page 14, lines 244-247: the authors should consider rewriting the sentences as it is difficult for the reader knows who they are referring to in 'We have a unique opportunity...' Are the authors referring to themselves, physiotherapists or healthcare professionals in general involved in COPD rehabilitation? Also, the study sample comprised patients who were not exclusively on admission to pulmonary rehabilitation programs.R: We have changed this sentence on Page 16 Lines 280-282 to, “Clinicians have a unique opportunity…” The reviewer is correct that our sample was not exclusively PR participants. Our intended meaning here is that measurement of participation may be a valuable addition to these programs because of the lower scores seen among people with COPD. There is a need to assess participation in people with COPD and to treat restrictions and PR programs might be the place to do that since patients are followed for an extended period of time. Clinicians in PR have a unique opportunity to address the longer-term consequences of the disease. Reviewer #3: Sachi O’Hoski et al aimed to compare participation scores in people with COPD to scores from a random sample of older adults using a validated measure of participation, the LLDI which is consistent with the concept of participation in the international classification of functioning, disability and health. LLDI sores were lower for the COPD group compared to controls for both the frequency and limitation domains of the LLDI. The paper is generally written in an excellent way, the description of methods used is clear, results are nicely presented and discussion is focused. However, the study is limited by its design.I have the following concerns.1. The authors used a secondary analysis of existing data to compare COPD patients and controls in terms of quality-of-life outcomes. Data are derived from two different time periods, one of the them during the COVID-19 pandemic. This type of design may have introduced biases in the accuracy of the results of this study.R: We have added that the control group’s social participation was likely impacted by the pandemic, “potentially explaining the smaller difference between groups in this subscale” (Page 14 Lines 226-227). We have also indicated this as a limitation on Page 16 Lines 268-276: “And finally, the control group completed the study during the first wave of the COVID-19 pandemic at which time there were social and public health restrictions in place. This difference in social circumstances might have impacted the frequency of participation in life tasks, making the control group results non-generalizable to non-pandemic times. The frequency of social activities was low in both groups and it is likely that the control group would have shown even higher scores on this subscale had public health restrictions not been in place at the time. As such, the differences seen in the participation scores between the two groups may have been attenuated due to temporal confounding.”2. During the pandemic many things occurred in terms of our living that may have affected subjects’ decisions and activities. In this respect activities and participation may have been different compared to the previous period- where COPD patients were recruited. How the authors treated this source of potential bias in their analysis? Has LLDI been validated during these circumstances? Or, do we know that this instrument is accurate even during periods with such different social conditions? It would be useful to know that LLDI provides similar results in similar populations but in different time periods/social conditions (or not).R: We have acknowledged that participation scores for the control group may have been higher had it not been for the pandemic and public health restrictions and indicated that this was a potential limitation. We have not adjusted our analyses for this temporal difference as our aim was to simply investigate the difference in scores between the groups. The LLDI has strong evidence for its psychometric properties in various populations and contexts  and while scores may differ based on a variety of factors such as external barriers to participation and participant choice, these factors are individual and are taken into account when one is answering the questions on the LLDI. While we have assumed that scores on some of the subscales would have been impacted by social restrictions, this should not impact the validity of the measure. In terms of comparison of scores in different social conditions, we have provided some information about scores found in the literature pre-pandemic on Pages 14 Lines 227-230: “Normative scores have not been established for the LLDI but two previous studies of community-dwelling adults aged 65 and over reported mean scores of 41.4 [19] and 45.5 [20] points on the social subscale, similar to the mean score of 47.2 points seen in our control group.” 3. In addition, COPD patients experience relatively severe disease based on the FEV1 reported. Is there a similar assessment of the respiratory function for controls?R: We do not have data on respiratory function for the control group. This was a secondary analysis of data so we were limited by what information was collected for the primary study. We have added this as a limitation on Pages 15-16 Lines 267-268: “In addition, we did not have pulmonary function test results from the control group participants and it is possible that some of them had undiagnosed respiratory disease.”4. Introduction could be shorter. I would highlight more -being more specific- the clinical value of the results of this study in the discussion sectionR: We have added to the discussion on Page 15 Lines 257-260: “The decreased frequency of and increased limitations in participation found in people with COPD highlights the importance of assessing this important aspect of health in this population and addressing participation restrictions as part of pulmonary rehabilitation in order mitigate negative sequalae such as psychological distress and mortality.”AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 13 Sep 2022People with COPD have greater participation restrictions than age-matched older adults without respiratory conditions assessed during the COVID-19 pandemicPONE-D-22-03462R1Dear Dr. Beauchamp,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Kind regards,Wanich SuksatanAcademic EditorPLOS ONEAdditional Editor Comments : <span style="color: rgb; font-family: verdana, geneva, arial, helvetica, sans-serif; font-size: 11.2px;"> Congratulations for successful amendments! </span>  26 Sep 2022PONE-D-22-03462R1 People with COPD have greater participation restrictions than age-matched older adults without respiratory conditions assessed during the COVID-19 pandemic Dear Dr. Beauchamp:I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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