A guide to interpreting a study of patient-reported outcomes

Outcomes measured from the patient perspective are particularly important in plastic surgery, where many of the treatments are aimed at improving physical function, psychosocial function, and quality of life. Understanding the measurement of patient-reported outcomes is critical to determine the value of the interventions performed, to better inform clinical decision-making, and to guide policy debates. It is critical that physicians understand their patients' individual values when making treatment and policy recommendations based on evidence. This guide outlines the questions that readers should ask when appraising literature using patient-reported outcomes.     

Gait Biomechanics and Patient-Reported Function as Predictors of Response to a Hip Strengthening Exercise Intervention in Patients with Knee Osteoarthritis

ObjectiveMuscle strengthening exercises have been shown to improve pain and function in adults with mild-to-moderate knee osteoarthritis, but individual response rates can vary greatly. Predicting individuals who respond and those who do not is important in developing a more efficient and effective model of care for knee osteoarthritis (OA). Therefore, the purpose of this study was to use pre-intervention gait kinematics and patient-reported outcome measures to predict post-intervention response to a 6-week hip strengthening exercise intervention in patients with mild-to-moderate knee OA.MethodsThirty-nine patients with mild-to-moderate knee osteoarthritis completed a 6-week hip-strengthening program and were subgrouped as Non-Responders, Low-Responders, or High-Responders following the intervention based on their change in Knee injury Osteoarthritis Outcome Score (KOOS). Predictors of responder subgroups were retrospectively determined from baseline patient-reported outcome measures and kinematic gait parameters in a discriminant analysis of principal components. A 3–4 year follow-up on 16 of the patients with knee OA was also done to examine long-term changes in these parameters.ResultsA unique combination of patient-reported outcome measures and kinematic factors was able to successfully subgroup patients with knee osteoarthritis with a cross-validated classification accuracy of 85.4%. Lower patient-reported function in daily living (ADL) scores and hip frontal plane kinematics during the loading response were most important in classifying High-Responders from other sub-groups, while a combination of hip, knee, ankle kinematics were used to classify Non-Responders from Low-Responders.ConclusionPatient-reported outcome measures and objective biomechanical gait data can be an effective method of predicting individual treatment success to an exercise intervention. Measuring gait kinematics, along with patient-reported outcome measures in a clinical setting can be useful in helping make evidence-based decisions regarding optimal treatment for patients with knee OA.     

Review of data describing outcomes that are used to assess changes in quality of life after reduction mammaplasty.

Although plastic surgeons have empirically "known" of the benefits of reduction mammaplasty for their patients, a paucity of outcome studies have been reported. For this study, an attempt to perform a meta-analysis of outcomes in reduction mammaplasty was undertaken. A computer literature search was performed of the MEDLINE database for the period between 1966 and September of 1997 for the Medical Subject Headings mammaplasty and outcome measures. Reference lists were used for additional reports. No trials were identified that met the criteria for meta-analysis. Seventeen publications met less restrictive review criteria that evaluated quality-of-life outcome measures. A systematic evaluation of patient-focused outcome measures demonstrated that consistent improvement in physical symptoms was found across most studies, as was a high degree of patient satisfaction (78 to 95 percent very or moderately satisfied), and some have shown improvement in body image and psychological well-being. However, although this review does identify consistent improvements in patient quality of life after reduction mammaplasty, inconsistencies among study designs do not allow formal meta-analysis.     

Quality of life measures in health care. I: Applications and issues in assessment.

Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.     

A new short form individual quality of life measure (SEIQoL-DW): application in a cohort of individuals with HIV/AIDS.

Quality of life is an increasingly important outcome measure in medicine and health care. Many measures of quality of life present patients with predetermined lists of questions that may or may not be relevant to the individual patient. This paper describes a brief measure, the SEIQoL-DW, which is derived from the schedule for evaluation of individual quality of life (SEIQoL). The measure allows respondents to nominate the areas of life which are most important, rate their level of functioning or satisfaction with each, and indicate the relative importance of each to their overall quality of life. Given its practicality and brevity, the measure should prove particularly useful in clinical situations where patient generated data on quality of life is important. This article describes the first clinical application of the measure, assessing the quality of life of a cohort of patients with HIV/AIDS managed in general practice.     

Measuring the quality of later life.

This paper examines quality of life as a scientific construct with a wide range of applications. The assessment of patients'' quality of life is assuming increasing importance in medicine and health care. Illnesses, diseases and their treatments can have significant impacts on such areas of functioning as mobility, mood, life satisfaction, sexuality, cognition and ability to fulfil occupational, social and family roles. The emerging quality of life construct may be viewed as a paradigm shift in outcome measurement since it shifts the focus of attention from symptoms to functioning. This holistic approach more clearly establishes the patient as the centre of attention and subsumes many of the traditional measures of outcome. Quality of life assessment is particularly relevant to ageing populations both for healthy elderly and for those who develop chronic diseases where maintenance of quality of life rather than cure may be the primary goal of treatment. This paper introduces the concept of quality of life and describes the significant difficulties in definition, measurement and interpretation that must be addressed before such measures can be used as reliable and valid indicators of disease impact and treatment outcomes. It is argued that approaches to quality of life assessment in the elderly should incorporate advances in knowledge about the psychological adaptation to ageing. Consequently, the unique perspective of the individual on his or her own quality of life must be incorporated into outcome assessments aimed at improving the quality of health care. Incorporating measures of subjective outcome such as quality of life into policy decisions on resource allocation in health care will prove one of the major challenges for health services over the next decade.     

Final Remarks

The author replies to the comments of Drs Blanchard and McGrady, urging that researchers reinvigorate their research efforts in complementary and alternative treatments for hypertension. In subsequent research there is a need to assess treatment adherence, to use more rigorous outcome measures, and to develop new outcome measures that assess impact and improvement in quality of life.     

A study of the impact of oral health on the quality of life of older people in the UK- findings from a National Survey.

Objectives The aim of this study was to was to determine whether older adults perceive oral health as affecting their life quality and to identify variations in impacts in relation to socio-demographic factors, dental service utilisation and method of payment. Design This study formed part of the Office for National Statistics Omnibus Survey, which utilised a random probability sample of addresses from the British Postcode Address File (PAF). Setting 3,000 homes were selected from one hundred post sectors across Britain. Respondents were interviewed in their homes about how oral health affects their quality of life. Subjects 454 older people (aged 65 and over) took part in the survey. Main outcome measures The study group perceived oral health as impacting on their quality of life in general (negative and/or positive impact) (70%, 318), enhancing (53%, 241) and detracting (44%, 199) from their life quality. The most frequently perceived way in which oral health affects life quality was its effect on eating and comfort. Older people from higher socio-economic groups reported that oral health had a greater impact on their quality of life in general (positive and/or negative impacts), (OR=1.77,95% CI= 1.22,2.78) and specifically, enhancing their quality of life (OR=1.52, 95% CI=1.01,2.30). Those who reported attending the dentist within the last year perceived that their oral health enhanced their life quality (OR=1.55, 95% CI=1.01,2.38). Conclusions Socio-economic background and dental attendance pattern are associated with how older people perceived oral health as affecting quality of life. These findings may have implications for promoting regular dental attendance and auditing dental services for older people.     

COPD symptoms in the morning: impact,evaluation and management

Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities. It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought. The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies. Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires. In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement. We also present available evidence on the effect of pharmacological therapies on morning symptoms.     

Brain Fog in Hypothyroidism: Understanding the Patient’s Perspective

ObjectivePatient-centered studies have shown that several patients on thyroid hormone replacement therapy for hypothyroidism exhibit persistent symptoms, including “brain fog.” Here, we aimed to determine which of these specific symptoms are associated with brain fog, identify patient-reported factors that modify these symptoms, and identify patient concerns related to brain fog not included in thyroid-specific questionnaires.MethodsA survey on brain fog symptoms adapted from thyroid-specific patient-reported outcome was distributed online. Textual data analysis was performed to identify common areas of concern from open-ended survey responses.ResultsA total of 5170 participants reporting brain fog while being treated for hypothyroidism were included in the analysis. Of these, 2409 (46.6%) participants reported symptom onset prior to the diagnosis of hypothyroidism, and 4096 (79.2%) participants experienced brain fog symptoms frequently. Of the symptoms listed, participants associated fatigue and forgetfulness most frequently with brain fog. More rest was the most common factor provided for improving symptoms. The textual data analysis identified areas of concern that are not often included in thyroid-specific quality of life questionnaires, including a focus on the diagnosis of hypothyroidism, the types and doses of medications, and the patient-doctor relationship.ConclusionBrain fog in patients treated for hypothyroidism was associated most frequently with fatigue and cognitive symptoms. Several additional areas of patient concern were found to be associated with brain fog, which are not typically addressed in thyroid-specific questionnaires.     

One hundred years ago: How to be happy though a doctor

ObjectivesTo assess the growth of quality of life measures and to examine the availability of measures across specialties.DesignSystematic searches of electronic databases to identify developmental and evaluative work relating to health outcome measures assessed by patients.Results3921 reports that described the development and evaluation of patient assessed measures met the inclusion criteria. Of those that were classifiable, 1819 (46%) were disease or population specific, 865 (22%) were generic, 690 (18%) were dimension specific, 409 (10%) were utility, and 62 (1%) were individualised measures. During 1990-9 the number of new reports of development and evaluation rose from 144 to 650 per year. Reports of disease specific measures rose exponentially. Over 30% of evaluations were in cancer, rheumatology and musculoskeletal disorders, and older people''s health. The generic measures—SF-36, sickness impact profile, and Nottingham health profile—accounted for 612 (16%) reports.ConclusionsIn some specialties there are numerous measures of quality of life and little standardisation. Primary research through the concurrent evaluation of measures and secondary research through structured reviews of measures are prerequisites for standardisation. Recommendations for the selection of patient assessed measures of health outcome are needed.

What is already known on this topic

Quality of life measures are increasingly used for measuring health outcomes in evaluative researchThere is little standardisation in the use of such measures within clinical trials

What this study adds

There has been exponential growth in reports relating to the development and evaluation of quality of life measuresThe number of reports varies considerably according to the health problem     

Symptom burden and health-related quality of life in chronic kidney disease: A global systematic review and meta-analysis

BackgroundThe importance of patient-reported outcome measurement in chronic kidney disease (CKD) populations has been established. However, there remains a lack of research that has synthesised data around CKD-specific symptom and health-related quality of life (HRQOL) burden globally, to inform focused measurement of the most relevant patient-important information in a way that minimises patient burden. The aim of this review was to synthesise symptom prevalence/severity and HRQOL data across the following CKD clinical groups globally: (1) stage 1–5 and not on renal replacement therapy (RRT), (2) receiving dialysis, or (3) in receipt of a kidney transplant.Methods and findingsMEDLINE, PsycINFO, and CINAHL were searched for English-language cross-sectional/longitudinal studies reporting prevalence and/or severity of symptoms and/or HRQOL in CKD, published between January 2000 and September 2021, including adult patients with CKD, and measuring symptom prevalence/severity and/or HRQOL using a patient-reported outcome measure (PROM). Random effects meta-analyses were used to pool data, stratified by CKD group: not on RRT, receiving dialysis, or in receipt of a kidney transplant. Methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, and an exploration of publication bias performed. The search identified 1,529 studies, of which 449, with 199,147 participants from 62 countries, were included in the analysis. Studies used 67 different symptom and HRQOL outcome measures, which provided data on 68 reported symptoms. Random effects meta-analyses highlighted the considerable symptom and HRQOL burden associated with CKD, with fatigue particularly prevalent, both in patients not on RRT (14 studies, 4,139 participants: 70%, 95% CI 60%–79%) and those receiving dialysis (21 studies, 2,943 participants: 70%, 95% CI 64%–76%). A number of symptoms were significantly (p < 0.05 after adjustment for multiple testing) less prevalent and/or less severe within the post-transplantation population, which may suggest attribution to CKD (fatigue, depression, itching, poor mobility, poor sleep, and dry mouth). Quality of life was commonly lower in patients on dialysis (36-Item Short Form Health Survey [SF-36] Mental Component Summary [MCS] 45.7 [95% CI 45.5–45.8]; SF-36 Physical Component Summary [PCS] 35.5 [95% CI 35.3–35.6]; 91 studies, 32,105 participants for MCS and PCS) than in other CKD populations (patients not on RRT: SF-36 MCS 66.6 [95% CI 66.5–66.6], p = 0.002; PCS 66.3 [95% CI 66.2–66.4], p = 0.002; 39 studies, 24,600 participants; transplant: MCS 50.0 [95% CI 49.9–50.1], p = 0.002; PCS 48.0 [95% CI 47.9–48.1], p = 0.002; 39 studies, 9,664 participants). Limitations of the analysis are the relatively few studies contributing to symptom severity estimates and inconsistent use of PROMs (different measures and time points) across the included literature, which hindered interpretation.ConclusionsThe main findings highlight the considerable symptom and HRQOL burden associated with CKD. The synthesis provides a detailed overview of the symptom/HRQOL profile across clinical groups, which may support healthcare professionals when discussing, measuring, and managing the potential treatment burden associated with CKD.Protocol registrationPROSPERO CRD42020164737.

In a systematic review and meta analysis, Benjamin R. Fletcher and colleagues study patient-reported symptom prevalence, severity, and health related quality of life among individuals with different stages of chronic kidney disease in 62 countries.     

Heterogeneity in Patient-Reported Outcomes following Low-Intensity Mental Health Interventions: A Multilevel Analysis

Background

Variability in patient-reported outcomes of psychological treatments has been partly attributed to therapists – a phenomenon commonly known as therapist effects. Meta-analytic reviews reveal wide variation in therapist-attributable variability in psychotherapy outcomes, with most studies reporting therapist effects in the region of 5% to 10% and some finding minimal to no therapist effects. However, all except one study to date have been conducted in high-intensity or mixed intervention groups; therefore, there is scarcity of evidence on therapist effects in brief low-intensity psychological interventions.

Objective

To examine therapist effects in low-intensity interventions for depression and anxiety in a naturalistic setting.

Data and Analysis

Session-by-session data on patient-reported outcome measures were available for a cohort of 1,376 primary care psychotherapy patients treated by 38 therapists. Outcome measures included PHQ-9 (sensitive to depression) and GAD-7 (sensitive to general anxiety disorder) measures. Three-level hierarchical linear modelling was employed to estimate therapist-attributable proportion of variance in clinical outcomes. Therapist effects were evaluated using the intra-cluster correlation coefficient (ICC) and Bayesian empirical predictions of therapist random effects. Three sensitivity analyses were conducted: 1) using both treatment completers and non-completers; 2) a sub-sample of cases with baseline scores above the conventional clinical thresholds for PHQ-9 and GAD-7; and 3) a two-level model (using patient-level pre- and post-treatment scores nested within therapists).

Results

The ICC estimates for all outcome measures were very small, ranging between 0% and 1.3%, although most were statistically significant. The Bayesian empirical predictions showed that therapist random effects were not statistically significantly different from each other. Between patient variability explained most of the variance in outcomes.

Conclusion

Consistent with the only other study to date in low intensity interventions, evidence was found to suggest minimal to no therapist effects in patient-reported outcomes. This draws attention to the more prominent source of variability which is found at the between-patient level.     

Effectiveness of home care programmes for patients with incurable cancer on their quality of life and time spent in hospital: systematic review

Objective: To investigate whether for patients with incurable cancer comprehensive home care programmes are more effective than standard care in maintaining the patients’ quality of life and reducing their “readmission time” (percentage of days spent in hospital from start of care till death). Design: Systematic review. Methods: A computer aided search was conducted using the databases of Medline, Embase, CancerLit, and PsychLit. The search for studies and the assessment of the methodological quality of the relevant studies were performed by two investigators, blinded from each other. Prospective, controlled studies investigating the effects of a home care intervention programme on patients’ quality of life or on readmission time were included in the analyses. Results: Only 9 prospective controlled studies were found; eight were performed in the United States and 1 in the United Kingdom. Their methodological quality was judged to be moderate (median rating 62 on a 100 point scale). None of the studies showed a negative influence of home care interventions on quality of life. A significantly positive influence on the outcome measures was seen in 2 out of the 5 studies measuring patients’ satisfaction with care, in 3/7 studies measuring physical dimensions of quality of life, in 1/6 studies measuring psychosocial dimensions, and in 2/5 studies measuring readmission time. The incorporation of team members’ visits to patients at home or regular multidisciplinary team meetings into the intervention programme seemed to be related to positive results. Conclusions: The effectiveness of comprehensive home care programmes remains unclear. Given the enormity of the problems faced by society in caring for patients with terminal cancer, further research is urgently needed.

Key messages

• Only nine controlled prospective studies have compared the effects of home care intervention programmes for patients with terminal cancer with those of standard care, in relation to patients’ quality of life and time spent in hospital between start of care and death
• The methodological quality of these studies seemed to be moderate
• Home care programmes did not have a negative influence on quality of life or time spent in hospital; some studies observed positive effects on these outcome measures
• Enabling team members to visit patients at home and holding regular multidisciplinary team meetings seem important elements for obtaining favourable results
• The general belief that home care programmes are effective for patients with terminal cancer is not supported scientifically

     

Effects of a comprehensive cardiac rehabilitation program on quality of life and exercise tolerance in women: A retrospective analysis

BACKGROUND: Currently, there are a lack of investigations that have examined the effect of participating in a comprehensive cardiac rehabilitation program on quality of life and physiological measures in women of different ages. The purpose of this investigation was to examine the effect of participating in a comprehensive cardiac rehabilitation program on quality of life, exercise tolerance, blood pressure and lipids in women between 33 and 82 years of age. METHODS: The 126 women participated in a 14-week cardiac rehabilitation program that consisted of 7 weeks of formal supervised exercise training and 7 weeks of unsupervised exercise and lifestyle modification. Physiologic and quality of life outcome measures obtained at the outset and after 14 weeks included: 1) exercise treadmill time; 2) resting and peak systolic and diastolic blood pressure; 3) total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and Triglycerides; 4) Cardiac Quality of Life Index questionnaire. RESULTS: Significant improvements were found in the following quality of life measures after participating in the cardiac rehabilitation program: physical well being, psychosocial, worry, nutrition and symptoms. No significant differences were seen for any QOL variable between the different age groups. Significant improvements were seen in exercise tolerance (+21%) and high density lipoprotein (+5%). CONCLUSION: Cardiac rehabilitation may play an important role in improving quality of life, exercise tolerance and high density lipoprotein cholesterol levels in younger and older women with underlying cardiovascular disease.     

Are Scores on English and French Versions of the PHQ-9 Comparable? An Assessment of Differential Item Functioning

Background

Medical research increasingly utilizes patient-reported outcome measures administered and scored in different languages. In order to pool or compare outcomes from different language versions, instruments should be measurement equivalent across linguistic groups. The objective of this study was to examine the cross-language measurement equivalence of the Patient Health Questionnaire-9 (PHQ-9) between English- and French-speaking Canadian patients with systemic sclerosis (SSc).

Methods

The sample consisted of 739 English- and 221 French-speaking SSc patients. Multiple-Indicator Multiple-Cause (MIMIC) modeling was used to identify items displaying possible differential item functioning (DIF).

Results

A one-factor model for the PHQ-9 fit the data well in both English- and French-speaking samples. Statistically significant DIF was found for 3 of 9 items on the PHQ-9. However, the overall estimate in depression latent scores between English- and French-speaking respondents was not influenced substantively by DIF.

Conclusions

Although there were several PHQ-9 items with evidence of minor DIF, there was no evidence that these differences influenced overall scores meaningfully. The PHQ-9 can reasonably be used without adjustment in Canadian English- and French-speaking samples. Analyses assessing measurement equivalence should be routinely conducted prior to pooling data from English and French versions of patient-reported outcome measures.     

Artichoke leaf extract reduces mild dyspepsia in an open study

A recent post-marketing study indicated that high doses of standardised artichoke leaf extract (ALE) may reduce symptoms of dyspepsia. To substantial these findings, this study investigated the efficacy of a low-dose ALE on amelioration of dyspeptic symptoms and improvement of quality of life. The study was an open, dose-ranging postal study. Healthy patients with self-reported dyspepsia were recruited through the media. The Nepean Dyspepsia Index and the State-Trait Anxiety Inventory were completed at baseline and after 2 months of treatment with ALE, which was randomly allocated to volunteers as 320 or 640 mg daily. Of the 516 participants, 454 completed the study. In both dosage groups, compared with baseline, there was a significant reduction of all dyspeptic symptoms, with an average reduction of 40% in global dyspepsia score. However, there were no differences in the primary outcome measures between the two groups, although relief of state anxiety, a secondary outcome, was greater with the higher dosage (P = 0.03). Health-related quality of life was significantly improved in both groups compared with baseline. We conclude that ALE shows promise to ameliorate upper gastro-intestinal symptoms and improve quality of life in otherwise healthy subjects suffering from dyspepsia.     

The thersites complex in plastic surgical patients

Body dysmorphic disorder describes the preoccupation with an imagined defect of appearance. A subgroup of patients suffer from the so-called Thersites complex, in which a minimal physical deformity causes excessive psychological disturbances and distress. Patients with body dysmorphic disorder tend primarily to visit a plastic surgeon for relief with distinct plans for surgical correction of their "deformity." Psychotherapy is generally refused or ineffective. The plastic surgeon should be familiar with this mental disorder and recognize these patients during consultation. Most of these patients should be excluded from surgery; however, patients of the Thersites complex category might be candidates for plastic surgical correction after careful selection. Only the experienced plastic surgeon should make the decision to operate in this situation. A successful treatment can relieve the patient from his or her distress and improve the quality of life substantially. A surgical result that is not accepted by the patient can end in a tragedy for either the patient or the doctor.     

Patient-orientated longitudinal study of multiple sclerosis in south west England (The South West Impact of Multiple Sclerosis Project,SWIMS) 1: protocol and baseline characteristics of cohort

Background  

There is a need for greater understanding of the impact of multiple sclerosis (MS) from the perspective of individuals with the condition. The South West Impact of MS Project (SWIMS) has been designed to improve understanding of disease impact using a patient-centred approach. The purpose is to (1) develop improved measurement instruments for clinical trials, (2) evaluate longitudinal performance of a variety of patient-reported outcome measures, (3) develop prognostic predictors for use in individualising drug treatment for patients, particularly early on in the disease course.     

Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial

Background

The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesised that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD.

Methods

In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations.

Results

Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups.

Conclusion

Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane.

Trial registration

ISRCTN07600011