Development and validation of reference equations for dual-energy x-ray absorptiometry-derived measures of fat-free mass in adults aged 45-85 years: Results from the Canadian Longitudinal Study on Aging.

Reference equations for fat-free (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy x-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45-85years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1,881 healthy participants (57%male) aged 55years [IQR: 50-61]. Reference equations performed comparably in the validation cohort and discriminated reference values between healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45-85 years.

Functional Recovery of Adults Following Acute COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to investigate the objective, functional recovery of patients more than 3 months after acute COVID-19 infection. METHODS: Comprehensive database searches of EMBASE, PubMed/MEDLINE, Cochrane COVID-19 Study Register, CINAHL, and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were carried out until October 19, 2022. Data were extracted and agreed in duplicate. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method. RESULTS: One-hundred six papers covering 20,063 patients who were either hospitalized or not hospitalized with acute COVID-19 who were followed-up between 3 to 24 months were included. Percentage predicted 6-minute walk distance at 3 months to <5 months was 84.3% (95% CI = 79.2-89.3; n = 21; I2 = 98.3%) and 92.5% (95% CI = 89.8-95.3; n = 9; I2 = 94.5%) at ≥11 months. Cardiopulmonary exercise testing revealed percentage predicted peak oxygen consumption rate ($peak\dot{\mathrm{V}}{\mathrm{o}}_2$) at 3 months to <5 months was 77.3% (95% CI = 71.0-83.7; n = 6; I2 = 92.3%) and 95.4% (95% CI = 87.1-103.6; n = 2; I2 = 77.3%) at ≥11 months. Mean handgrip strength was greatest at ≥11 months at 31.16 kg (95% CI = 19.89-42.43; n = 2; I2 = 98.3%) of all time points. All analyses showed marked heterogeneity. CONCLUSION: Patients have reduced physical function more than 3 months after COVID-19 infection. Better physical function in multiple physical domains is found after a longer recovery time. IMPACT: Physical function as measured by the 6-minute walk test, hand grip strength, and cardiopulmonary exercise testing is reduced at 3 months after COVID-19 infection and can remain over 11 months of follow-up. This protracted recovery following acute COVID-19 infection supports the need to assess physical function at any clinical follow-up, and further research into rehabilitation programs and intervention for patients who have not recovered.

Do pulmonary rehabilitation programmes improve outcomes in patients with COPD posthospital discharge for exacerbation: a systematic review and meta-analysis.

INTRODUCTION: Previous systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to examine the efficacy of pulmonary rehabilitation programmes initiated within 3 weeks of hospital discharge following an exacerbation of COPD. METHODS: An update of a previous Cochrane review was undertaken using the Cochrane Airways Review Group Specialised Register. Searches were conducted from October 2015 to August 2023 for studies that initiated pulmonary rehabilitation within 3 weeks of hospital discharge. Studies assessing the impact of solely inpatient pulmonary rehabilitation were excluded. Forest plots were generated using a generic inverse variance random effects method. RESULTS: Seventeen studies were included. Posthospital discharge pulmonary rehabilitation reduced hospital re-admissions (OR 0.48, 95% CI 0.30 to 0.77, I2=67%), improved exercise capacity (6 min walk test, mean difference (MD) 57 m, 95% CI 29 to 86, I2=89%; incremental shuttle walk test, MD 43 m, 95% CI 6 to 79, I2=81%), health-related quality of life (St. George's Respiratory Questionnaire, MD -8.7 points, 95% CI -12.5 to -4.9, I2=59%; Chronic Respiratory Disease Questionnaire (CRQ)-emotion, MD 1.0 points, 95% CI 0.4 to 1.6, I2=74%; CRQ-fatigue, MD 0.9 points, 95% CI 0.1 to 1.6, I2=91%), and dyspnoea (CRQ-dyspnoea, MD 1.0 points, 95% CI 0.3 to 1.7, I2=87%; modified Medical Research Council Dyspnoea Scale, MD -0.3 points, 95% CI -0.5 to -0.1, I2=60%). Significant effects were not observed for CRQ-mastery, COPD assessment test, EuroQol-5 Dimension-5 Level and mortality. No intervention-related adverse events were reported. DISCUSSION: Pulmonary rehabilitation delivered posthospital discharge for exacerbation of COPD results in a reduction in hospital re-admissions and improvements in exercise capacity, health-related quality of life and dyspnoea in the absence of any intervention-related adverse events. TRIAL REGISTRATION NUMBER: CRD42023406397.

A fully automated pipeline for the extraction of pectoralis muscle area from chest computed tomography scans.

Background: Computed tomography (CT)-derived pectoralis muscle area (PMA) measurements are prognostic in people with or at-risk of COPD, but fully automated PMA extraction has yet to be developed. Our objective was to develop and validate a PMA extraction pipeline that can automatically: 1) identify the aortic arch slice; and 2) perform pectoralis segmentation at that slice. Methods: CT images from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study were used for pipeline development. Aorta atlases were used to automatically identify the slice containing the aortic arch by group-based registration. A deep learning model was trained to segment the PMA. The pipeline was evaluated in comparison to manual segmentation. An external dataset was used to evaluate generalisability. Model performance was assessed using the Dice-Sorensen coefficient (DSC) and PMA error. Results: In total 90 participants were used for training (age 67.0±9.9 years; forced expiratory volume in 1 s (FEV1) 93±21% predicted; FEV1/forced vital capacity (FVC) 0.69±0.10; 47 men), and 32 for external testing (age 68.6±7.4 years; FEV1 65±17% predicted; FEV1/FVC 0.50±0.09; 16 men). Compared with manual segmentation, the deep learning model achieved a DSC of 0.94±0.02, 0.94±0.01 and 0.90±0.04 on the true aortic arch slice in the train, validation and external test sets, respectively. Automated aortic arch slice detection obtained distance errors of 1.2±1.3 mm and 1.6±1.5 mm on the train and test data, respectively. Fully automated PMA measurements were not different from manual segmentation (p>0.05). PMA measurements were different between people with and without COPD (p=0.01) and correlated with FEV1 % predicted (p<0.05). Conclusion: A fully automated CT PMA extraction pipeline was developed and validated for use in research and clinical practice.

Pulmonary Rehabilitation for Adults with Chronic Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Despite the known benefits of pulmonary rehabilitation (PR) for patients with chronic respiratory disease, this treatment is underused. Evidence-based guidelines should lead to greater knowledge of the proven benefits of PR, highlight the role of PR in evidence-based health care, and in turn foster referrals to and more effective delivery of PR for people with chronic respiratory disease. Methods: The multidisciplinary panel formulated six research questions addressing PR for specific patient groups (chronic obstructive pulmonary disease [COPD], interstitial lung disease, and pulmonary hypertension) and models for PR delivery (telerehabilitation, maintenance PR). Treatment effects were quantified using systematic reviews. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel made the following judgments: strong recommendations for PR for adults with stable COPD (moderate-quality evidence) and after hospitalization for COPD exacerbation (moderate-quality evidence), strong recommendation for PR for adults with interstitial lung disease (moderate-quality evidence), conditional recommendation for PR for adults with pulmonary hypertension (low-quality evidence), strong recommendation for offering the choice of center-based PR or telerehabilitation for patients with chronic respiratory disease (moderate-quality evidence), and conditional recommendation for offering either supervised maintenance PR or usual care after initial PR for adults with COPD (low-quality evidence). Conclusions: These guidelines provide the basis for evidence-based delivery of PR for people with chronic respiratory disease.

Efficacy of interventions to alter measures of fat-free mass in people with COPD: a systematic review and meta-analysis.

Introduction: Low fat-free mass (FFM) is linked to poor health outcomes in COPD, including impaired exercise tolerance and premature death. The aim of this systematic review was to synthesise evidence on the effectiveness of interventions for increasing FFM in COPD. Methods: Searches of electronic databases (MEDLINE, Cochrane Library, Embase, Web of Science, Scopus) and trial registers (ClinicalTrials.gov) were undertaken from inception to August 2022 for randomised studies of interventions assessing measures of FFM in COPD. The primary outcome was change in FFM (including derivatives). Secondary outcomes were adverse events, compliance and attrition. Results: 99 studies (n=5138 people with COPD) of 11 intervention components, used alone or in combination, were included. Exercise training increased mid-thigh cross-sectional area (k=3, standardised mean difference (SMD) 1.04, 95% CI 0.02-2.06; p=0.04), but not FFM (k=4, SMD 0.03, 95% CI -0.18-0.24; p=0.75). Nutritional supplementation significantly increased FFM index (k=11, SMD 0.31, 95% CI 0.13-0.50; p<0.001), but not FFM (k=19, SMD 0.16, 95% CI -0.06-0.39; p=0.16). Combined exercise training and nutritional supplementation increased measures related to FFM in 67% of studies. Anabolic steroids increased FFM (k=4, SMD 0.98, 95% CI 0.24-1.72; p=0.009). Neuromuscular electrical stimulation increased measures related to FFM in 50% of studies. No interventions were more at risk of serious adverse events, low compliance or attrition. Discussion: Exercise training and nutritional supplementation were not effective in isolation to increase FFM, but were for localised muscle and index measures, respectively. Combined, exercise and nutritional supplementation shows promise as a strategy to increase FFM in COPD. Anabolic steroids are efficacious for increasing FFM in COPD.

Multilayer spintronic neural networks with radiofrequency connections.

Spintronic nano-synapses and nano-neurons perform neural network operations with high accuracy thanks to their rich, reproducible and controllable magnetization dynamics. These dynamical nanodevices could transform artificial intelligence hardware, provided they implement state-of-the-art deep neural networks. However, there is today no scalable way to connect them in multilayers. Here we show that the flagship nano-components of spintronics, magnetic tunnel junctions, can be connected into multilayer neural networks where they implement both synapses and neurons thanks to their magnetization dynamics, and communicate by processing, transmitting and receiving radiofrequency signals. We build a hardware spintronic neural network composed of nine magnetic tunnel junctions connected in two layers, and show that it natively classifies nonlinearly separable radiofrequency inputs with an accuracy of 97.7%. Using physical simulations, we demonstrate that a large network of nanoscale junctions can achieve state-of-the-art identification of drones from their radiofrequency transmissions, without digitization and consuming only a few milliwatts, which constitutes a gain of several orders of magnitude in power consumption compared to currently used techniques. This study lays the foundation for deep, dynamical, spintronic neural networks.

Suppression of crystallization in saline drop evaporation on pinning-free surfaces.

For sessile droplets of pure liquid on a surface, evaporation depends on surface wettability, the surrounding environment, contact angle hysteresis, and surface roughness. For non-pure liquids, the evaporation characteristics are further complicated by the constituents and impurities within the droplet. For saline solutions, this complication takes the form of a modified partial vapor pressure/water activity caused by the increasing salt concentration as the aqueous solvent evaporates. It is generally thought that droplets on surfaces will crystallize when the saturation concentration is reached, i.e., 26.3% for NaCl in water. This crystallization is initiated by contact with the surface and is thus due to surface roughness and heterogeneities. Recently, smooth, low contact angle hysteresis surfaces have been created by molecular grafting of polymer chains. In this work, we hypothesize that by using these very smooth surfaces to evaporate saline droplets, we can suppress the crystallization caused by the surface interactions and thus achieve constant volume droplets above the saturation concentration. In our experiments, we used several different surfaces to examine the possibility of crystallization suppression. We show that on polymer grafted surfaces, i.e., Slippery Omniphobic Covalently Attached Liquid-like (SOCAL) and polyethyleneglycol(PEGylated) surfaces, we can achieve stable droplets as low as 55% relative humidity at 25 °C with high reproducibility using NaCl in water solutions. We also show that it is possible to achieve stable droplets above the saturation concentration on other surfaces, including superhydrophobic surfaces. We present an analytical model, based on water activity, which accurately describes the final stable volume as a function of the initial salt concentration. These findings are important for heat and mass transfer in relatively low humidity environments.

The Association between Fat-Free Mass and Exercise Test Outcomes in People with Chronic Obstructive Pulmonary Disease: A Systematic Review.

People with chronic obstructive pulmonary disease (COPD) tend to have abnormally low levels of fat-free mass (FFM), which includes skeletal muscle mass as a central component. The purpose of this systematic review was to synthesise available evidence on the association between FFM and exercise test outcomes in COPD. MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus were searched. Studies that evaluated exercise-related outcomes in relation to measures of FFM in COPD were included. Eighty-three studies, containing 18,770 (39% female) COPD participants, were included. Considerable heterogeneity was identified in the ways that FFM and exercise test outcomes were assessed; however, higher levels of FFM were generally associated with greater peak exercise capacity. This association was stronger for some exercise test outcomes (e.g. peak rate of oxygen consumption during incremental cycle exercise testing) than others (e.g. six-minute walking distance). This review identified heterogeneity in the methods used for measuring FFM and exercise capacity. There was, in general, a positive association between FFM and exercise capacity in COPD. There was also an identified lack of studies investigating associations between FFM and temporal physiological and perceptual responses to exercise. This review highlights the significance of FFM as a determinant of exercise capacity in COPD.

Patient-related outcomes in patients referred to a respiratory clinic with persisting symptoms following non-hospitalised COVID-19.

Survivors of COVID-19 can present with varied and persisting symptoms, regardless of hospitalisation. We describe the ongoing symptoms, quality of life and return to work status in a cohort of non-hospitalised COVID-19 survivors with persisting respiratory symptoms presenting to clinic, who consented and completed patient-reported outcome measures. We identified fatigue, reduced quality of life and dysregulated breathing alongside the breathlessness. Those with co-existent fatigue had worse mood and quality of life and were less likely to have returned to normal working arrangements compared to those without fatigue. For non-hospitalised people with persisting symptoms following COVID-19 referred to a respiratory assessment clinic, there was a need for a wider holistic assessment, including return to work strategies.

Non-volatile artificial synapse based on a vortex nano-oscillator.

In this work, a new mechanism to combine a non-volatile behaviour with the spin diode detection of a vortex-based spin torque nano-oscillator (STVO) is presented. Experimentally, it is observed that the spin diode response of the oscillator depends on the vortex chirality. Consequently, fixing the frequency of the incoming signal and switching the vortex chirality results in a different rectified voltage. In this way, the chirality can be deterministically controlled via the application of electrical signals injected locally in the device, resulting in a non-volatile control of the output voltage for a given input frequency. Micromagnetic simulations corroborate the experimental results and show the main contribution of the Oersted field created by the input RF current density in defining two distinct spin diode detections for different chiralities. By using two non-identical STVOs, we show how these devices can be used as programmable non-volatile synapses in artificial neural networks.

The burden of chronic respiratory diseases in adults in Nepal: A systematic review.

While chronic lung disease causes substantial global morbidity and mortality, global estimates have primarily been based on broad assumptions. Specific country data from low-income countries such as Nepal are limited. This review assessed primary evidence on chronic respiratory disease burden among adults in Nepal. A systematic search was performed in June 2019 (updated May 2020) for studies through nine databases. High levels of heterogeneity deemed a narrative synthesis appropriate. Among 27 eligible studies identified, most were low-moderate quality with cross-sectional and retrospective study design. Chronic lung diseases identified were chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis and restrictive lung diseases. Studies were categorised as: (i) community-based, (ii) hospital-based and (iii) comorbidity-related and disease burden. Reported disease prevalence varied widely (COPD, 1.67-14.3%; asthma, 4.2-8.9%). The prevalence of airflow obstruction was higher among rural dwellers (15.8%) and those exposed to household air pollution from domestic biomass burning as opposed to liquid petroleum gas users (Odds Ratio: 2.06). Several comorbidities, including hypertension and diabetes mellitus added to the disease burden. The review shows limited literature on lung disease burden in Nepal. Publications varied in terms of overall quality. Good quality research studies with prospective cohorts related to respiratory conditions are required.

Efficacy of unsupervised exercise in adults with obstructive lung disease: a systematic review and meta-analysis.

INTRODUCTION: The benefits of unsupervised exercise programmes in obstructive lung disease are unclear. The aim of this systematic review was to synthesise evidence regarding the efficacy of unsupervised exercise versus non-exercise-based usual care in patients with obstructive lung disease. METHODS: Electronic databases (MEDLINE, CINAHL, Embase, Allied and Complementary Medicine Database, Web of Science, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database) and trial registers (ClinicalTrials.gov, Current Controlled Trials, UK Clinical Trials Gateway and WHO International Clinical Trials Registry Platform) were searched from inception to April 2020 for randomised trials comparing unsupervised exercise programmes with non-exercise-based usual care in adults with chronic obstructive pulmonary disease (COPD), non-cystic fibrosis bronchiectasis or asthma. Primary outcomes were exercise capacity, quality of life, mortality, exacerbations and respiratory cause hospitalisations. RESULTS: Sixteen trials (13 COPD, 2 asthma, 1 chronic bronchitis: 1184 patients) met the inclusion criteria. Only data on COPD populations were available for meta-analysis. Unsupervised exercise resulted in a statistically but not clinically significant improvement in the 6-Minute Walk Test (n=5, MD=22.0 m, 95% CI 4.4 to 39.6 m, p=0.01). However, unsupervised exercise did lead to statistically significant and clinically meaningful improvements in St. George's Respiratory Questionnaire (n=4, MD=-11.8 points, 95% CI -21.2 to -2.3 points, p=0.01) and Chronic Respiratory Disease Questionnaire domains (dyspnoea: n=4, MD=0.5 points, 95% CI 0.1 to 0.8 points, p<0.01; fatigue: n=4, MD=0.7 points, 95% CI 0.4 to 1.0 points, p<0.01; emotion: n=4, MD=0.5 points, 95% CI 0.2 to 0.7 points, p<0.01; mastery: unable to perform meta-analysis) compared with non-exercise-based usual care. DISCUSSION: This review demonstrates clinical benefits of unsupervised exercise interventions on health-related quality of life in patients with COPD. High-quality randomised trials are needed to examine the effectiveness of prescription methods.

Questionnaires or Serum Immunoglobulin G Testing in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease.

Rationale: Hypersensitivity pneumonitis (HP) results from exposure to a variety of stimuli, which are challenging to identify. Questionnaires and serum immunoglobulin G (IgG) testing are methods to identify potentially causative exposures.Objectives: To perform a systematic review to determine the usefulness of questionnaires and serum IgG testing in identifying exposures that may have caused HP.Methods: This systematic review informed an international, multidisciplinary panel that developed a clinical practice guideline on the diagnosis of HP for the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax. MEDLINE, the Cochrane Library, and EMBASE were searched from January 1946 to October 2019 for studies that used a questionnaire or serum IgG testing to identify exposures that may have caused HP. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to appraise the quality of the evidence.Results: Searches identified 1,141 and 926 potentially relevant articles for questionnaires and serum IgG testing, respectively. The full texts of 32 and 49 articles, respectively, were reviewed. Two observational studies for questionnaires and 15 accuracy studies for serum IgG testing were selected. Questionnaires were better at detecting potentially relevant exposures than clinical history (100% vs. 26%; risk ratio [RR], 3.80; 95% confidence interval [95% CI], 1.79-8.06) and serum IgG testing (100% vs. 63%; RR, 1.58; 95% CI, 1.12-2.23) but did not differ from serum IgG testing plus bronchial challenge testing (59% vs. 65%; RR, 0.90; 95% CI, 0.65-1.24). Longer, detailed questionnaires were more likely to lead to identification of potential exposures. Only 70% of potential exposures identified by questionnaires were subsequently confirmed by environmental testing. Serum IgG testing distinguished HP from healthy exposed and unexposed control subjects with high sensitivity (90% and 92%, respectively) and high specificity (91% and 100%, respectively) but did not distinguish HP as effectively from interstitial lung diseases (ILDs; sensitivity of 83% and specificity of 68%).Conclusions: Using a questionnaire may help clinicians identify potentially relevant exposures when evaluating a patient with newly identified ILD for HP. Serum IgG testing may also lead to identification of potentially relevant exposures, but its usefulness for distinguishing HP from other types of ILD is poor.

Coldzyme® Mouth Spray reduces duration of upper respiratory tract infection symptoms in endurance athletes under free living conditions.

Upper respiratory tract infection (URTI) can compromise athlete preparation and performance, so countermeasures are desirable. The aim of this study was to assess the effects of ColdZyme® Mouth Spray (ColdZyme) on self-reported upper respiratory tract infection in competitive endurance athletes under free-living conditions. One hundred and twenty-three endurance-trained, competitive athletes (recruited across 4 sites in England, UK) were randomised to control (no treatment, n = 61) or ColdZyme (n = 62) for a 3-month study period (between December 2017 and March 2018; or December 2018 and April 2019). They recorded daily training and illness symptoms (Jackson common cold questionnaire) during the study period. A total of 130 illness episodes were reported during the study with no difference in incidence between groups (episodes per person: 1.1 ± 0.9 Control, 1.0 ± 0.8 ColdZyme, P = 0.290). Episode duration was significantly shorter in ColdZyme compared to Control: Control 10.4 ± 8.5 days vs. ColdZyme 7.7 ± 4.0 days, P = 0.016). Further analysis to compare episodes with poor vs. good compliance with ColdZyme instructions for use (IFU) within the ColdZyme group showed a greater reduction in duration of URTI when compliance was good (9.3 ± 4.5 days in ColdZyme poor IFU compliance vs. 6.9 ± 3.5 days in ColdZyme good IFU compliance, P = 0.040). ColdZyme may be an effective countermeasure to reduce URTI duration, which was significantly lower (by 26-34%) in the ColdZyme treatment group (with no influence on incidence). This may have implications for athlete performance.

Transbronchial Biopsy and Cryobiopsy in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease.

Rationale: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) with a diagnosis based on clinical, radiological, and pathological findings. The evidence supporting transbronchial forceps lung biopsy (TBBx) and transbronchial lung cryobiopsy (TBLC) as sampling techniques to diagnose HP in patients with newly detected ILD has not been reviewed systematically.Objectives: A systematic review was performed to assess the diagnostic yield and complication rates of TBBx or TBLC in patients with newly detected ILD whose differential diagnosis includes HP and to inform the development of the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of HP.Methods: Medline, Excerpta Medica Database, and the Cochrane Library were searched through October 2019. Studies that enrolled patients with ILD and reported the diagnostic yield of TBBx or TBLC were selected for inclusion. Data related to diagnostic yield and safety outcomes were extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation (GRADE) approach.Results: The histopathologic diagnostic yields (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBBx and TBLC were 37% (95% confidence interval [CI], 32-42%) and 82% (95% CI, 78-86%), respectively, among patients with ILD. Among those diagnosed by TBBx, the proportion with HP could not be determined. However, among those diagnosed by TBLC, 13.4% had HP. TBBx was complicated by moderate to severe bleeding, severe bleeding, and pneumothorax in 4% (95% CI, 0-8%), 0% (95% CI, 0-1%), and 7% (95% CI, 2-13%) of patients, respectively. TBLC was complicated by any bleeding, severe bleeding, and pneumothorax in 11% (95% CI, 7-15%), 0% (95% CI, 0-1%), and 11% (95% CI, 9-14%) of patients, respectively. The quality of the evidence was very low because of the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results.Conclusions: Very low-quality evidence indicated that TBLC had a higher diagnostic yield than TBBx among patients with ILD, although complications were similar.

Bronchoalveolar Lavage Lymphocytes in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease.

Rationale: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by inflammation and/or fibrosis in response to an inhalational exposure.Objectives: To determine the value of bronchoalveolar lavage (BAL) fluid lymphocyte cellular analysis in the detection of HP among patients with newly detected ILD.Methods: This systematic review was undertaken in the context of development of an American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guideline. The clinical question was, "should patients with newly detected ILD undergo BAL fluid lymphocyte analysis to diagnose HP?" MEDLINE, EMBASE, and the gray literature were searched through October 2019. Studies that reported the percentage of BAL fluid lymphocytes for various ILDs were selected for inclusion. Meta-analyses compared the mean percentage of BAL fluid lymphocytes among patients with HP with that among patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. The sensitivity and specificity by which various percentages of BAL fluid lymphocytes distinguish HP from IPF and sarcoidosis were also evaluated.Results: Eighty-four articles were selected. No randomized trials or observational studies were identified that compared BAL fluid lymphocyte analysis with no BAL fluid lymphocyte analysis in patients with ILD. Included studies were case series describing BAL fluid cell differentials in patients with various ILDs. The percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared with IPF. Similarly, the percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared with sarcoidosis. A threshold of 20% BAL fluid lymphocytes distinguished fibrotic HP from IPF with a sensitivity and specificity of 69% and 61%, respectively, and nonfibrotic HP from IPF with a sensitivity and specificity of 95% and 61%, respectively. It distinguished fibrotic HP from sarcoidosis with a sensitivity and specificity of 69% and 26%, respectively, and nonfibrotic HP from sarcoidosis with a sensitivity and specificity of 95% and 26%, respectively.Conclusions: The percentage of BAL fluid lymphocytes is higher in HP than IPF or sarcoidosis. However, a threshold that distinguishes HP from IPF or sarcoidosis with both high sensitivity and high specificity was not identified.

Inflammatory responses to acute exercise during pulmonary rehabilitation in patients with COPD.

OBJECTIVE: Pulmonary rehabilitation is a cornerstone treatment in the management of chronic obstructive pulmonary disease (COPD). Acute bouts of exercise can lead to short bursts of inflammation in healthy individuals. However, it is unclear how COPD patients respond to acute bouts of exercise. This study assessed inflammatory responses to exercise in COPD patients at the start (phase 1) and end (phase 2) of pulmonary rehabilitation. METHODS: Blood samples were collected before and after an acute exercise bout at the start (phase 1, n = 40) and end (phase 2, n = 27) of pulmonary rehabilitation. The primary outcome was change in fibrinogen concentrations. Secondary outcomes were changes in CRP concentrations, total/differential leukocyte counts, markers of neutrophil activation (CD11b, CD62L and CD66b), and neutrophil subsets (mature, suppressive, immature, progenitor). RESULTS: Acute exercise (phase 1) did not induce significant changes in fibrinogen (p = 0.242) or CRP (p = 0.476). Total leukocyte count [mean difference (MD), 0.5 ± 1.1 (109 L-1); p = 0.004], neutrophil count [MD, 0.4 ± 0.8 (109 L-1); p < 0.001], and immature neutrophils (MD, 0.6 ± 0.8%; p < 0.001) increased post-exercise. Neutrophil activation markers, CD11b (p = 0.470), CD66b (p = 0.334), and CD62L (p = 0.352) were not significantly altered post-exercise. In comparison to the start of pulmonary rehabilitation (phase 2), acute exercise at the end of pulmonary rehabilitation led to a greater fibrinogen response (MD, 84 mg/dL (95% CI - 14, 182); p = 0.045). CONCLUSION: An acute bout of exercise does not appear to induce significant alterations in the concentrations of inflammatory mediators but can increase white blood cell subsets post-exercise. A greater fibrinogen response to acute exercise is seen at the end of pulmonary rehabilitation when compared to the start. Further research is required to understand the clinical context of these acute inflammatory responses to exercise.