Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.

BACKGROUND: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). METHODS: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. RESULTS: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. CONCLUSION: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.

Improving Assessment and Learning Environments for Graduate Medical Trainees to Advance Healthcare Language Equity.

Language-appropriate care is critical for equitable, high-quality health care, but educational standards to assure graduate medical trainees are prepared to give such care are lacking. Detailed guidance for graduate medical education is provided by the Accreditation Council for Graduate Medical Education through the following: (1) an assessment framework for competencies, subcompetencies, and milestones for trainees and (2) the Clinical Learning Environment Review (CLER) Pathways for assessment of trainees' learning environments. These tools do not include a robust framework to evaluate trainees' abilities to offer language-appropriate care. They also do not address the learning environment's potential to support such care. A multidisciplinary group of linguistic, medical, and educational experts drafted a new subcompetency with milestones and an expanded CLER Pathway to highlight the importance of equitable care for patients who prefer languages other than English. These resources offer residency and fellowship programs tools to guide assessment, curriculum development, and learning-environment improvements related to language-appropriate care. Recognizing that programs have unique needs and resources, we propose a range of initial actions to address language equity. A focus on language diversity in the learning environment can have a broad and lasting impact on care quality, patient safety, and health equity.

Teaching foundational language equity concepts in the pre-clinical curriculum.

BACKGROUND: Despite the prevalence of non-English languages in the US population, existing medical training to teach communication with linguistically diverse communities is limited to electives or solely focuses on medical interpreting. Language-appropriate communication skills are seldom comprehensively integrated in medical education. This study describes the development and evaluation of an intervention to teach foundational language equity concepts. METHODS: The authors implemented a pre-clinical language equity course at three medical school campuses between August 2020 and March 2022. Sessions focused on the impact of language in health, physician language proficiency standards, and working with medical interpreters. The study sought to (1) understand students' language skills and prior clinical experiences with patients with non-English language preference and (2) evaluate the curriculum's impact. Students self-reported their language skills and experiences as part of a voluntary pre-questionnaire. Pre and post-questionnaires evaluated knowledge, attitudes, and intent to apply language equity concepts. Descriptive statistics and chi-squared tests were used to examine trends; themes were identified from free-text responses. RESULTS: Overall, 301 students completed the course, 252 (83%) completed at least one questionnaire; for each session, between 35% and 46% of learners completed both pre and post-questionnaires. Three quarters (189/252) reported non-English languages. Over half (138/252) reported previous non-English language patient care, and 28% (62/224) had served as ad hoc (untrained) interpreters. Only two students (< 1%) had ever been assessed for medical language abilities. Students demonstrated improved post-course language equity knowledge, strategies for interpreter-mediated encounters, and likelihood to report a plan for language skills assessment (all p < .001). Most plans were multifaceted (61%, 38/62), involving goals like completing a language course, taking a proficiency exam, openly discussing skills and uncertainties with team members, and increasing professional interpreter utilization. CONCLUSIONS: A longitudinal language equity curriculum can be feasibly integrated in pre-clinical education, highlight the linguistic diversity of the student body, and serve as a first step in ensuring that all students have a strong language equity foundation prior to clinical rotations. Future steps include evaluating the intervention's potential long-term effects on professional interpreter utilization, student clinical performance, and institutional culture that promotes multilingualism.

Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.

BACKGROUND: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID). METHODS: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. RESULTS: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence. CONCLUSIONS: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.

Validity Evidence for the Physician Oral Language Observation Matrix as a Measure of Medical Spanish Proficiency.

BACKGROUND: The lack of a standardized language assessment process for medical students and physicians communicating in a non-English language threatens healthcare quality and safety. OBJECTIVE: To evaluate the validity of a new rating tool, the Physician Oral Language Observation Matrix (POLOM)™, in assessing medical students' oral communication with Spanish-speaking standardized patients (SPs). DESIGN: POLOM scores were compared to measures of student medical Spanish proficiency to examine convergent validity and to measures of clinical performance to examine concurrent/criterion validity. PARTICIPANTS: Forty-two students at two schools completed SP encounters between January 2021 and April 2022, and POLOM raters scored the videorecorded performances between January and June 2022. MAIN MEASURES: Two approaches to generating POLOM total scores were investigated: rater average and strict consensus. Convergent validity was examined via the POLOM's correlations with (1) the phone-based Clinician Cultural and Linguistic Assessment (CCLA) and (2) the self-rated Interagency Language Roundtable scale for healthcare (ILR-H). Concurrent/criterion validity was examined via correlations with (1) the Comunicación y Habilidades Interpersonales (CAI) scale, (2) a checklist completed by the SP, and (3) a faculty rating of the student's post-encounter clinical note. Pearson's correlations of r ≥ 0.5 and r ≥ 0.2 were considered evidence of convergent validity and concurrent/criterion validity, respectively. KEY RESULTS: Both rater average and strict consensus POLOM scores were strongly correlated with ILR-H (r = 0.72) and CCLA (r ≥ 0.60), providing evidence of convergent validity. The POLOM was substantially correlated with the CAI (r ≥ 0.29), the SP Checklist (r = 0.32), and the faculty scoring of the student's clinical note (r ≥ 0.24), providing concurrent/criterion validity evidence. CONCLUSIONS: The POLOM has demonstrated evidence of convergent and concurrent/criterion validity as a measure of medical students' Spanish proficiency during SP encounters. Additional research is needed to evaluate how the POLOM can be implemented with resident and practicing physicians, applied to other health professions, and adapted to other languages.

Description of two new species of Nostoc (Nostocales, Cyanobacteria) from central Mexico, using morphological, ecological, and molecular attributes.

The present study describes two new Nostoc species, N. montejanii and N. tlalocii, based on a polyphasic approach that combines morphological, ecological, and genetic characteristics. The five investigated populations, including those from newly collected material from central Mexico, were observed to possess morphological features characteristic of the Nostoc genus. Results showed that both new species are strictly associated with running water, and they show clear differences in their habitat preferences. The 16S rRNA gene sequences of the five strains displayed between 98% and 99% similarity to the genus Nostoc sensu stricto. The 16S rRNA gene phylogenetic analyses inferred using Bayesian inference, maximum likelihood, and parsimony methods, placed these five strains in two separate clades distinct from other Nostoc species. The secondary structures of the 16S-23S internal transcribed spacer rRNA region in the two new species showed >10.5% dissimilarities in the operons when compared with other Nostoc species. In addition, clear morphological differences were observed between the two Mexican species, including the color of the colonies (black in N. montejanii and green in N. tlalocii), the size of the cells (greater in N. montejanii), and the number of polyphosphate granules present in the cells (one in N. montejanii and up to four in N. tlalocii).

Post-Intensive Care Unit Multidisciplinary Approach in Patients with Severe Bilateral SARS-CoV-2 Pneumonia.

Background: Short and long-term sequelae after admission to the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19) are to be expected, which makes multidisciplinary care key in the support of physical and cognitive recovery. Objective: To describe, from a multidisciplinary perspective, the sequelae one month after hospital discharge among patients who required ICU admission for severe COVID-19 pneumonia. Design: Prospective cohort study. Environment: Multidisciplinary outpatient clinic. Population: Patients with severe COVID-19 pneumonia, post- ICU admission. Methods: A total of 104 patients completed the study in the multidisciplinary outpatient clinic. The tests performed included spirometry, measurement of respiratory muscle pressure, loss of body cell mass (BCM) and BCM index (BCMI), general joint and muscular mobility, the short physical performance battery (SPPB or Guralnik test), grip strength with hand dynamometer, the six-minute walk test (6-MWT), the functional assessment of chronic illness therapy-fatigue scale (FACIT-F), the European quality of life-5 dimensions (EQ-5D), the Barthel index and the Montreal cognitive assessment test (MoCA). While rehabilitation was not necessary for 23 patients, 38 patients attended group rehabilitation sessions and other 43 patients received home rehabilitation. Endpoints: The main sequelae detected in patients were fatigue (75.96%), dyspnoea (64.42%) and oxygen therapy on discharge (37.5%). The MoCA showed a mean score compatible with mild cognitive decline. The main impairment of joint mobility was limited shoulder (11.54%) and shoulder girdle (2.88%) mobility; whereas for muscle mobility, lower limb limitations (16.35%) were the main dysfunction. Distal neuropathy was present in 23.08% of patients, most frequently located in lower limbs (15.38%). Finally, 50% of patients reported moderate limitation in the EQ-5D, with a mean score of 60.62 points (SD 20.15) in perceived quality of life. Conclusions: Our findings support the need for a multidisciplinary and comprehensive evaluation of patients after ICU admission for COVID-19 because of the wide range of sequelae, which also mean that these patients need a long-term follow-up. Impact on clinical rehabilitation: This study provides data supporting the key role of rehabilitation during the follow-up of severe patients, thus facilitating their reintegration in society and a suitable adaptation to daily living.

Medical Student Perceptions of Sociocultural Issues in Healthcare: A Multisite Study of Medical Spanish Education.

THEORY: Cultural competence and humility are core elements of medical education in a diverse society. Language is inseparable from culture, as language informs, indexes, frames, and encodes both culture and worldview. Spanish is the most common non-English language taught in U.S. medical schools, yet medical Spanish courses tend to artificially separate language from culture. It is unknown to what extent medical Spanish courses advance students' sociocultural knowledge or patient care skills. HYPOTHESES: Based on current predominant pedagogy, medical Spanish classes may not adequately integrate sociocultural issues relevant to Hispanic/Latinx health. We hypothesized that students who completed a medical Spanish course would not demonstrate significant gains in sociocultural skills following the educational intervention. METHOD: An interprofessional team developed a sociocultural questionnaire, and 15 medical schools invited their students to complete the questionnaire before and after completing a medical Spanish course. Of participating schools, 12 implemented a standardized medical Spanish course and three served as control sites. Survey data were analyzed regarding: (1) perceived sociocultural competence (recognition of common cultural beliefs, recognition of culturally normative non-verbal cues, gestures, and social behaviors, ability to address sociocultural issues in healthcare context, and knowledge of health disparities); (2) application of sociocultural knowledge; and (3) demographic factors and self-rated language proficiency (Poor, Fair, Good, Very Good, or Excellent) on the Interagency Language Roundtable scale for healthcare (ILR-H). RESULTS: Overall, 610 students participated in sociocultural questionnaire between January 2020 and January 2022. After the course, participants reported an increased understanding of cultural aspects of communication with Spanish-speaking patients and the ability to apply sociocultural knowledge to patient care (all p < 0.001). When analyzed by demographic factors, students who identified as Hispanic/Latinx or as heritage speakers of Spanish tended to report increased sociocultural knowledge/skills following the course. When examined by Spanish proficiency, preliminary trends showed that students at both ILR-H Poor and Excellent levels did not demonstrate gains in sociocultural knowledge or ability to apply sociocultural skills. Students at sites with a standardized course were likely to improve sociocultural skills in mental health conversations (p < 0.001) while students at control sites were not (p = 0.05). CONCLUSIONS: Medical Spanish educators may benefit from additional guidance on teaching sociocultural aspects of communication. Our findings support that students at ILR-H levels of Fair, Good, and Very Good are particularly well-suited for gaining sociocultural skills in current medical Spanish courses. Future studies should explore potential metrics to evaluate cultural humility/competence within actual interactions with patients.

An Overview of Online Resources for Medical Spanish Education for Effective Communication with Spanish-Speaking Patients.

PHENOMENON: Despite the rapid development of virtual medical Spanish educational materials, online resources lack transparency and a peer-review process. The purpose of this interdisciplinary study was to provide a critical inventory of virtual resources for medical Spanish education, thereby providing a panorama of the current state of online medical Spanish. APPROACH: Research team members conducted iterative searches to identify medical Spanish online resources, which were then screened for predetermined inclusion/exclusion criteria. Between June and August 2020, a panel of medical and language experts then adapted and applied a previously published evaluation tool to determine whether resources that met study criteria would help learners achieve medical Spanish core competencies and to what extent each resource incorporated communicative language activities. Consensus meetings were conducted to resolve disagreements and identify gaps in online education. FINDINGS: Out of 465 resources, 127 were further screened, and eight were selected for evaluation. Medical and language specialists independently scored each resource and, following discussions, achieved consensus. Overall, no resource met suitability criteria for all five medical Spanish learner competencies or cultural elements, and only one was suitable for achieving the self-assessment competency. INSIGHTS: Interdisciplinary consensus meetings provide an important avenue for resolving differences of opinion and for integrating both language and medical perspectives into the evaluation process. Existing online resources should be used in conjunction with other materials to ensure that all core competencies for medical Spanish education are addressed. This study revealed important gaps in online resources, including a need to target advanced Spanish learners, apply authentic communicative activities, include assessment opportunities, and integrate culture in the learning program. Based on the current state of online medical Spanish, we offer recommendations for future resources.

Medical Spanish in US Medical Schools: a National Survey to Examine Existing Programs.

BACKGROUND: Most medical schools offer medical Spanish education to teach patient-physician communication skills with the growing Spanish-speaking population. Medical Spanish courses that lack basic standards of curricular structure, faculty educators, learner assessment, and institutional credit may increase student confidence without sufficiently improving skills, inadvertently exacerbating communication problems with linguistic minority patients. OBJECTIVE: To conduct a national environmental scan of US medical schools' medical Spanish educational efforts, examine to what extent existing efforts meet basic standards, and identify next steps in improving the quality of medical Spanish education. DESIGN: Data were collected from March to November 2019 using an IRB-exempt online 6-item primary and 14-item secondary survey. PARTICIPANTS: All deans of the Association of American Medical Colleges member US medical schools were invited to complete the primary survey. If a medical Spanish educator or leader was identified, that person was sent the secondary survey. MAIN MEASURES: The presence of medical Spanish educational programs and, when present, whether the programs met four basic standards: formal curricular structure, faculty educator, learner assessment, and course credit. KEY RESULTS: Seventy-nine percent of medical schools (125 out of 158) responded to either or both the primary and/or secondary surveys. Among participating schools, 78% (98/125) of medical schools offered medical Spanish programming; of those, 21% (21/98) met all basic standards. Likelihood of meeting all basic standards did not significantly differ by location, school size, or funding type. Fifty-four percent (53/98) report formal medical Spanish curricula, 69% (68/98) have faculty instructors, 57% (56/98) include post-course assessment, and 31% (30/98) provide course credit. CONCLUSIONS: Recommended next steps for medical schools include formalizing medical Spanish courses as electives or required curricula; hiring and/or training faculty educators; incorporating learner assessment; and granting credit for student course completion. Future studies should evaluate implementation strategies to establish best practice recommendations beyond basic standards.

Mapping IPF helps identify geographic regions at higher risk for disease development and potential triggers.

BACKGROUND AND OBJECTIVE: The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis (IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross-analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development. METHODS: This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data. RESULTS: In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent. CONCLUSION: In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.

Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.

A Mechanism-Based Sphingosine-1-phosphate Lyase Inhibitor.

The synthesis of a series of vinylated analogues of sphingosine-1-phosphate together with their unambiguous configurational assignment by VCD methods is reported. Among them, compound RBM10-8 can irreversibly inhibit human sphingosine-1-phosphate lyase (hS1PL) while behaving also as an enzyme substrate. These findings, together with the postulated mechanism for S1PL activity, reinforce the role of RBM10-8 as a new mechanism-based hS1PL inhibitor.

Long-term efficacy and effectiveness of a behavioural and community-based exercise intervention (Urban Training) to increase physical activity in patients with COPD: a randomised controlled trial.

There is a need to increase and maintain physical activity in patients with chronic obstructive pulmonary disease (COPD). We assessed 12-month efficacy and effectiveness of the Urban Training intervention on physical activity in COPD patients.This randomised controlled trial (NCT01897298) allocated 407 COPD patients from primary and hospital settings 1:1 to usual care (n=205) or Urban Training (n=202). Urban Training consisted of a baseline motivational interview, advice to walk on urban trails designed for COPD patients in outdoor public spaces and other optional components for feedback, motivation, information and support (pedometer, calendar, physical activity brochure, website, phone text messages, walking groups and a phone number). The primary outcome was 12-month change in steps·day-1 measured by accelerometer.Efficacy analysis (with per-protocol analysis set, n=233 classified as adherent to the assigned intervention) showed adjusted (95% CI) 12-month difference +957 (184-1731) steps·day-1 between Urban Training and usual care. Effectiveness analysis (with intention-to-treat analysis set, n=280 patients completing the study at 12 months including unwilling and self-reported non-adherent patients) showed no differences between groups. Leg muscle pain during walks was more frequently reported in Urban Training than usual care, without differences in any of the other adverse events.Urban Training, combining behavioural strategies with unsupervised outdoor walking, was efficacious in increasing physical activity after 12 months in COPD patients, with few safety concerns. However, it was ineffective in the full population including unwilling and self-reported non-adherent patients.

Ischiocrural Strength May Be a Better Prognostic Marker Than Quadriceps Strength in COPD.

It is well known that chronic obstructive pulmonary disease (COPD) patients present with muscle dysfunction that may not correlate with the degree of severity of airflow obstruction. Historically, the strength deficit of the knee extensor musculature (quadriceps) has been described as an independent factor of mortality in COPD. We present the results of a retrospective study with longitudinal follow-up of 60 patients with severe COPD followed for 7 years. During follow-up 22 patients died, mainly of respiratory cause. We have observed that the strength of knee flexor muscles (ischiocrural) and dominant handgrip were independent predictors of mortality in severe COPD patients. However, knee extensor strength (quadriceps) was not an independent predictor of mortality. This is the first study which highlights the importance of knee flexor musculature as a prognostic factor in COPD.