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Currently, there is no consensus regarding indication and benefits of Kinesio Taping® on pulmonary function of individuals with chronic obstructive pulmonary disease (COPD).To identify the effects of Kinesio Taping® on pulmonary function of individuals with COPD through a systematic review and meta-analysis.Systematic review including experimental or quasi-experimental studies in English, Portuguese, or Spanish. Searches were conducted on LILACS, Scielo, Medline, Web of Science, and Scopus databases. Two reviewers independently conducted study selection, data extraction, and analysis. Methodological quality was assessed using PEDro scale, while meta-analyses were conducted using RevMan software. This review was registered (PROSPERO CRD42020223752).Five studies were included. Forced expiratory volume in the first second (FEVResults suggest that Kinesio Taping® does not improve pulmonary function of individuals with COPD.

Although vaping has recently increased as a mode of inhaling marijuana and has been associated with numerous and sometimes fatal cases of acute severe lung injury, smoking remains the most common method of inhaling marijuana and has been studied more extensively. Smoking marijuana has been shown to produce modest but significant short-term bronchodilation both in healthy subjects and in those with asthma. Long-term effects of habitual marijuana smoking include the following: (1) symptoms of chronic bronchitis (increased cough, sputum production, and wheezing); (2) modest effects on lung function in cross-sectional studies (no significant decrease in FEV

Sarcoidosis is a multiorgan granulomatous disease with a variable course.The purpose of this study is to identify the patients that are more likely to experience disease progression.A retrospective study in patients ≥18 years. Pulmonary function and radiological stage (Scadding criteria) were assessed at diagnosis, and at 1, 3 and 5 years. Sarcoidosis progression was established based on deterioration of radiological or pulmonary function (decrease ≥10% of FVC and/or ≥15% of diffusing capacity of the lung (DLCO).The sample included 277 caucasian patients [mean age, 50±13.6; 69.7% between 31-60 years; 56.3% men]. In total, 65% had stage II sarcoidosis, whereas only 8.3% had stage III/IV disease. Mean pulmonary function (FVC, FEVAt 3 years, a third of patients experienced sarcoidosis progression. Age was the only factor associated with disease prognosis.

There is a strong association between nutrition and long-term FEV1 in cystic fibrosis (CF), but studies have been driven by data from subjects with pancreatic insufficiency (PI-CF). We thus evaluated the association between body mass index (BMI) and FEV1 percent-predicted (FEV1pp) in children with pancreatic sufficiency (PS-CF) and contrasted it with the association in PI-CF.We utilized data from the CF Foundation Patient Registry. The cohort included children born 1995-2010, diagnosed2 years of age, and who had annualized data on BMI percentile and FEV1pp at ages 6-16 years. Pancreatic status was defined based on pancreatic enzyme replacement therapy. The association between BMI and FEV1 was evaluated using linear and mixed-effects longitudinal regression.There were 424 children with PS-CF and 7,849 with PI-CF. The association between BMI and FEV1 differed significantly by pancreatic status: each 10-pct higher BMI was associated with 2% [95%CI = 1.9-2.1] higher FEV1pp in PI-CF, compared to just 0.9% [0.5-1.3] in PS-CF (PIn children with PS-CF, BMI remains an important determinant of lung function. However, it may be less critical to attain a BMI50

Rationale and Objectives To evaluate associations between longitudinal changes of quantitative CT parameters and spirometry in patients with fibrotic hypersensitivity pneumonitis (HP). Materials and Methods Serial CT images and spirometric data were retrospectively collected in a group of 25 fibrotic HP patients. Quantitative CT analysis included histogram parameters (median, interquartile range, skewness, and kurtosis) and a pretrained convolutional neural network (CNN)-based textural analysis, aimed at quantifying the extent of consolidation (C), fibrosis (F), ground-glass opacity (GGO), low attenuation areas (LAA) and healthy tissue (H). Results At baseline, FVC was 61(44-70) %pred. The median follow-up period was 1.4(0.8-3.2) years, with 3(2-4) visits per patient. Over the study, 8 patients (32%) showed a FVC decline of more than 5%, a significant worsening of all histogram parameters (p≤0.015) and an increased extent of fibrosis via CNN (p=0.038). On histogram analysis, decreased skewness and kurtosis were the parameters most strongly associated with worsened FVC (respectively, r2=0.63 and r2=0.54, p

A decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis.This retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed.Of the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74.A 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a growing prevalence. We aimed to evaluate the effects of co-supplementation with vitamins C, E, and D on respiratory, inflammatory, and oxidative stress outcomes in IPF patients.Thirty-three patients participated in this quasi-experimental study and were supplemented with vitamins E, C, and D with 200 IU/daily, 250 mg/every other day and 50000 IU/Weekly, respectively for 12 weeks. Anthropometric indices, dietary recall, physical activity, Saint George questionnaire were assessed along with the biochemical measures of inflammation and oxidative stress, and respiratory parameters. Data were analyzed by SPSS version 21, and P-value ≤ 0.05 was considered significant.Results of spirometry and plethysmography tests showed a significant increase in FEV1 (P-value = 0.016), IRV (P-value = 0.001), RV (P-value = 0.002) and TLC (P-value = 0.003). But no significant change was observed in FVC, VC, FEV1/FVC, and ERV. We also found that ESR, hs-CRP, TGFβ, and PrC remarkably reduced after the supplementation (P-value ≤ 0.05), while the GPx level remained unchanged.It is concluded that three months of supplementation with a combination of D, C, and E vitamins in IPF patients may positively affect the respiratory function and alleviate the inflammation and oxidative stress.

A cardiopulmonary exercise test (CPET) is ideally suited to quantify exercise tolerance and evaluate the pathophysiological mechanism(s) of dyspnea and exercise limitation in people with chronic respiratory disease. Although there are several statements on CPET and many outstanding resources detailing the cardiorespiratory and perceptual responses to exercise, limited information is available to support the health care provider in conducting a practical CPET evaluation. This article provides the health care provider with practical and timely information on how to use CPET data to understand dyspnea and exercise intolerance in people with chronic respiratory diseases. Information on CPET protocol, as well as how to evaluate maximal patient effort, peak rate of oxygen consumption, ventilatory demand, pulmonary gas exchange, ventilatory reserve, operating lung volumes, and exertional dyspnea, is presented. Two case examples are also described to highlight how these parameters are evaluated to provide a clinical interpretation of CPET data.

In 2017, Nkam et al. published a prognostic score to predict death or lung transplant within 3 years among adult cystic fibrosis (CF) patients. Their model was developed using French CF registry data and was subsequently validated in the Canadian CF registry. We evaluated this prognostic score using data from adult patients with CF in the United States (US) CF Foundation Patient registry, combined with lung transplant records from the United Network for Organ Sharing (UNOS) Registry (2013 to 2016) (n=11,542). We found that the prognostic score had a very good discriminative index predicting death or lung transplant in the US CF population (AUC 0.88, 95% CI 0.88-0.89) with an odds ratio (OR) of 2.83 (95% CI 2.69 – 2.97) for each unit increase in the score. However, it did not provide significant additional utility over an FEV1 ≤30% of predicted as a predictor of death or lung transplant.

RATIONALE: Low body mass index (BMI) may influence lung transplant decisions for patients with advanced cystic fibrosis (CF) lung disease. OBJECTIVE: Determine whether patients with advanced CF lung disease and BMI ≤17 kg/m(2) are less likely to be listed for lung transplant or have a higher risk of death without listing compared to those with higher BMI. METHODS: Using merged United Network for Organ Sharing and CF Foundation Patient Registries, we identified adults with onset of advanced lung disease (FEV(1) ≤ 40% predicted) between May-2005 and December-2016. We analyzed survival using competing risks regression with cause-specific risks of listing for lung transplant and death without listing. BMI ≤ 17 kg/m(2) was our predictor. MEASUREMENTS AND MAIN RESULTS: Among 5,121 CF patients with advanced lung disease, 23% were listed for lung transplant (n=1,201), 23% died without listing (n=1,190), and 44% were alive without listing (n=2,730) as of December-2016. Patients with BMI ≤ 17 kg/m(2) were less likely to be listed for transplant (HR 0.69; 95% CI 0.57, 0.83) and more likely to die without listing (HR 1.63; 95% CI 1.41, 1.88). We identified important regional variations in the likelihood of referral and listing, based on BMI. CONCLUSIONS: Patients with advanced CF lung disease and BMI ≤ 17 kg/m(2) are less likely to be listed for lung transplant and have a higher risk of dying without listing, compared to those with higher BMI. Regional differences suggest access to transplant for malnourished CF patients may be limited by location.

Rheumatoid arthritis (RA) is a connective tissue disease, characterized by symmetric peripheral polyarthritis. Extra-articular disease occurs in approximately 50% of the patients with lung being a common site. The presence of functional or morphological abnormalities in small airways has recently been noted in patients with RA but its exact prevalence and clinical significance is still a subject of debate. This study was aimed to determine the prevalence of small airway disease (SAD) in patients with RA and the factors influencing it.Fifty consecutive patients with RA were included in this cross-sectional observational study. All patients were subjected to pulmonary function tests (PFT) including Spirometry and Forced Oscillation technique (FOT). Those with features of SAD on PFT were subjected to High-Resolution Computed Tomography (HRCT) of the chest.Spirometry was suggestive of SAD in 17 patients, with 34% prevalence and FOT was abnormal in 9 patients, with 18% prevalence in the study population. Of 17 patients with SAD on spirometry, 8 (47.05%) patients showed mosaic attenuation, a sign of SAD on the HRCT chest. On univariate analysis, age, Disease Activity Score (DAS-28), joint erosions on X-ray, RF and anti-CCP were found to be associated with SAD.SAD was present in one-third of the patients with RA, even in those with short duration of disease, low to moderate disease activity and no respiratory symptoms. It is thus inferred that the complete workup of RA patients should include pulmonary function assessment.

Background With an increase in published reports on respiratory rehabilitation (RR) in severe acute respiratory syndrome (SARS), there is a need for a meta-analysis and systematic review to measure the effects of the RR in SARS. Objective Objective of the review was to evaluate the efficacy and safety of RR in patients recovering from SARS. Methods PubMed/ MEDLINE, CENTRAL, EMBASE, and Clinical Trial Registries were systematically searched (between January 1, 2003, to July 31, 2021) to identify all patients who received RR, at least for six days, following SARS. The primary outcome was exercise capacity [6-meter walking distance (6-MWD)], and secondary outcomes were change in pulmonary function test (PFT) parameters, activities in daily livings (ADLs), and quality of life (QoL). Meta-analysis was performed by using RevMan 5.4. Results Twenty-one observational studies, including eight comparative studies, were included. Eight comparative studies participated in quantitative meta-analysis. The intervention group, who received RR, improved significantly in exercise capacity (6-MWD) [mean difference (MD):45.79, (95% CI:31.66–59.92)] and PFT parameters, especially in forced vital capacity (FVC%) [MD:4.38, (95% CI:0.15–8.60)], and diffusion lung capacity for carbon monoxide (DLCO%) [MD:11.78, (95% CI:5.10–18.46)]. The intervention group failed to demonstrate significant improvement in ADLs and QoL outcomes. No significant adverse events were reported during the intervention. Conclusion Respiratory rehabilitation can improve exercise capacity and PFT parameters in patients recovering from SARS infection. The RR does not cause serious adverse events. Clinical trials to determine the best RR program (in terms of initiation, duration, and components) in SARS and its treatment efficacy, both in the short and long- term are needed.

Pectus excavatum is a frequent thoracic malformation increasingly treated with minimally invasive methods (MIRPE), which are performed for cardio-respiratory problems and in some centers also for esthetic considerations. Theoretically, MIRPE may increase thoracic elastic recoil, work of breathing and cause emphysema. The aim of the present study was to determine whether teenagers who underwent MIRPE may expect normal thoracic cage development, cardio-respiratory function, exercise capacity and asymptomatic functioning.Fifty five patients (21.1 ​± ​3.0 years) who underwent MIRPE between 2000 and 2010 were assessed 6.8 (±2.4) years after surgery. Controls were matched for sex, age and height to the intervention participants. Spirometry, body plethysmography, diffusion capacity and the 6 ​min walking test (6MWT) were performed. Anteroposterior (AP) and transverse chest diameters were measured.Participants who underwent MIRPE had normal pulmonary function, and exercise capacity. After adjustment for potential confounders, the intervention group had lower mean BMI [-1.88 ​± ​0.56 (kg/mYoung adults who undergo MIRPE may expect normal pulmonary function and exercise capacity. Observed differences in air trapping require further assessment in terms of emphysema development risk.

Background Anti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear. Methods A literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation. Results A total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86–0.97, I2 = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV1 from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, −0.86, 95% CI, −1.92 – 0.19, I2 = 0%; FEV1, mean difference, 0.01, 95% CI, −0.01 – 0.03, I2 = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99–1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72–1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85–1.01) when compared with the placebo. Conclusion Anti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.

Chronic hypersensitivity pneumonitis (cHP) is a heterogeneous condition, where both small airway involvement and fibrosis may simultaneously occur. Computer-aided analysis of CT lung imaging is increasingly used to improve tissue characterization in interstitial lung diseases (ILD), quantifying disease extension, and progression. We aimed to quantify via a convolutional neural network (CNN) method the extent of different pathological classes in cHP, and to determine their correlation to pulmonary function tests (PFTs) and mosaic attenuation pattern.The extension of six textural features, including consolidation (C), ground glass opacity (GGO), fibrosis (F), low attenuation areas (LAA), reticulation (R) and healthy regions (H), was quantified in 27 cHP patients (age: 56 ± 11.5 years, forced vital capacity [FVC]% = 57 ± 17) acquired at full-inspiration via HRCT. Each class extent was correlated to PFTs and to mosaic attenuation pattern.H showed a positive correlation with FVC%, FEV1% (forced expiratory volume), total lung capacity%, and diffusion of carbon monoxide (DLCO)% (r = 0.74, r = 0.78, r = 0.73, and r = 0.60, respectively, p0.001). GGO, R and C negatively correlated with FVC% and FEV1% with the highest correlations found for R (r = -0.44, and r = -0.46 respectively, p0.05); F negatively correlated with DLCO% (r = -0.42, p0.05). Patients with mosaic attenuation pattern had significantly more H (p = 0.04) and lower R (p = 0.02) and C (p = 0.0009) areas, and more preserved lung function indices (higher FVC%; p = 0.04 and DLCO%; p = 0.05), but did not show more air trapping in lung function tests.CNN quantification of pathological tissue extent in cHP improves its characterization and shows correlation with PFTs. LAA can be overestimated by visual, qualitative CT assessment and mosaic attenuation pattern areas in cHP represents patchy ILD rather than small-airways disease.

Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS).From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded.A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P .001), but lung function variables in the continuous SAPB group were significantly higher (P .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P.05).Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

Limited research exists regarding nonpharmacologic management of pulmonary arterial hypertension (PAH), except for exercise training. The objective of this study was to investigate the effects of osteopathic manipulative treatment (OMT) alone and combined with respiratory training on fractional exhaled nitric oxide (FeNO), and cardiopulmonary function in patients with PAH. This single-blind, prospective, randomized controlled study included 54 patients with PAH who were randomly allocated to OMT, combined intervention, and control groups. The OMT group (n = 16) and combined intervention group (n = 16) received OMT and yoga respiratory training plus OMT, respectively, twice a week for 8 weeks. The control group (n = 16) received no intervention. All patients undertook an educational lecture. FeNO level, pulmonary function, 6-minute walk distance (6MWD), maximal inspiratory and expiratory pressures, and handgrip strength were assessed at baseline and 8 weeks. Combined intervention and OMT groups significantly improved all outcome measures after 8 weeks of treatment (p0.01), except mean forced expiratory flow between 25% and 75% of forced vital capacity, which did not change in the OMT group (p0.05). The control group showed significant deteriorations in 6MWD, inspiratory and peripheral muscle strength, and pulmonary function except peak expiratory flow at 8 weeks (p0.05). The combined intervention group revealed significantly greater improvements of FeNO, 6MWD, respiratory and peripheral muscle strength, and pulmonary function except mean forced expiratory flow between 25% and 75% of forced vital capacity compared with the OMT group (p0.05). All outcomes significantly improved in both intervention groups versus the control group (p0.05). Our study demonstrated that adding respiratory training to OMT provided further benefit to FeNO level and cardiopulmonary function compared with OMT alone and that the OMT might be a useful and safe intervention for patients who cannot attend cardiac rehabilitation programs.

A 21-year-old male college student presented for a second opinion with low alpha-1 antitrypsin (AAT) levels and complaints of episodic dyspnea with wheezing and cough. He was a never smoker with a medical history of frequent respiratory tract infections in early childhood and allergy to dander, dust mites, peanuts, and eggs. There was no travel history outside of the continental United States. His mother had asthma. His symptoms were not controlled on inhaled corticosteroids and bronchodilators. His AAT genotype was found to be PI∗SZ, and augmentation therapy (with pooled human-plasma derived AAT) was recommended locally.

Despite being an important patient group, adult cystic fibrosis patients with an FEV1 below 40%predicted have been excluded from clinical trials with elexacaftor/tezacaftor/ivacaftor. We conducted a real-life 3 months follow-up study in 14 adult CF patients (median FEV1 34%predicted) demonstrating significant treatment effects in terms of FEV1 (an increase of 12%predicted at 4 weeks, remaining stable thereafter). Corresponding decreases in lung clearance index LCI (by 31%predicted, down from baseline 247%predicted) and ventilation heterogeneity in the acinar compartment (Sacin) (by 411%predicted, down from baseline 798%predicted) suggest a distinct peripheral lung effect. One patient had intermittent treatment interruptions because of drug-induced liver injury. Our real-life data confirm that treatment with elexacaftor/tezacaftor/ivacaftor is effective in severely obstructive patients, and this is the first study to show time evolution of ventilation distribution improvement, pointing to the peripheral lung as the main site of treatment effect.

Background Lower socioeconomic status (SES) has consistently been associated with poorer outcomes in individuals with cystic fibrosis (CF). Previous studies have compared outcomes for children with and without private insurance coverage, however the potential role of changes in insurance status on early health outcomes in children with CF remains unknown. Objectives To describe the variability in insurance status in early childhood and to evaluate whether insurance variability was associated with poorer outcomes at age 6. Methods Retrospective observational study using the Cystic Fibrosis Foundation Patient Registry. Insurance status was defined as: always private (including Tricare), exclusively public, or intermittent private insurance (private insurance and exclusively public insurance in separate years) during the first 6 years of life. Outcomes at age 6 included body mass index (BMI) and FEV1 percent predicted (maxFEV1pp). Results From a 2000–2011 birth cohort (n = 8,109), 42.3% always had private insurance, 30.0% had exclusively public insurance, and 27.6% had intermittent private insurance. BMI percentiles did not differ between groups; however, children with intermittent private insurance and exclusively public insurance had a 3.3% and 6.6% lower maxFEV1pp at age 6, respectively, compared to those with always private insurance. Conclusions A substantial proportion of young children in a modern CF cohort have public or intermittent private insurance coverage. While public insurance has been associated with poorer health outcomes in CF, variability in health insurance coverage may also be associated with an intermediate risk of disparities in lung function as early as age 6.

Background There are few clinically useful circulating biomarkers of lung function and lung disease. We hypothesized that genome-wide association studies (GWAS) of circulating proteins in conjunction with GWAS of pulmonary traits represents a clinically relevant approach to identifying causal proteins and therapeutically useful insights into mechanisms related to lung function and disease. Study Question Can an integrative genomic strategy using GWAS of plasma soluble receptor for advanced glycation end-products (sRAGE) levels in conjunction with GWAS of lung function traits identify putatively causal relations of sRAGE to lung function? Study Design and Methods Plasma sRAGE levels were measured in 6,861 Framingham Heart Study participants and GWAS of sRAGE was conducted to identify protein quantitative trait loci (pQTL), including cis-pQTL variants at the sRAGE protein-coding gene locus (AGER). We integrated sRAGE pQTL variants with variants from GWAS of lung traits. Colocalization of sRAGE pQTL variants with lung trait GWAS variants was conducted, and Mendelian randomization was performed using sRAGE cis-pQTL variants to infer causality of sRAGE for pulmonary traits. Cross-sectional and longitudinal protein-trait association analyses were conducted for sRAGE in relation to lung traits. Results Colocalization identified shared genetic signals for sRAGE with lung traits. Mendelian randomization analyses suggested protective causal relations of sRAGE to several pulmonary traits. Protein-trait association analyses demonstrated higher sRAGE levels to be cross-sectionally and longitudinally associated with preserved lung function. Interpretation sRAGE is produced by type I alveolar cells, and it acts as a decoy receptor to block the inflammatory cascade. Our integrative genomics approach provides evidence for sRAGE as a causal and protective biomarker of lung function, and the pattern of associations is suggestive of a protective role of sRAGE against restrictive lung physiology. We speculate that targeting the AGER/sRAGE axis may be therapeutically beneficial for the treatment and prevention of inflammation-related lung disease.

Objective The Outcome Measures in Rheumatology (OMERACT) is a research organization focused on improving health care outcomes for patients with autoimmune and musculoskeletal diseases. The Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Working Group on Lung Physiology is a group within OMERACT charged with identifying outcome measures that should be implemented in studies of patients with CTD-ILD. The OMERACT Filter 2.1 is an evidence-based algorithm used to identify outcome measures that are truthful, feasible, and able to discriminate between groups of interest. Our objective was to summate evidence (published literature, key opinion leader input, patient perspectives) that would influence the CTD-ILD Working Group's vote to accept or reject the use of two measures of lung physiology, the forced vital capacity (FVC) and the diffusion capacity of carbon monoxide (DLco) for use in randomized controlled trials (RTCs) and longitudinal observational studies (LOSs) involving patients with systemic sclerosis associated ILD (SSc-ILD). Methods Patient Research Partners (those afflicted with SSc-ILD) and the CTD-ILD Working Group on Lung Physiology were polled to assess their opinion on the FVC and DLco in terms of feasibility; the CTD-ILD Working Group was also queried on these instruments’ face and content validity. We then conducted a systematic literature review to identify articles in the SSc-ILD population that assessed the following measurement properties of FVC and DLco: (1) construct validity, (2) test-retest reliability, (3) longitudinal construct validity, (4) clinical trial discrimination/sensitivity to detect change in clinical trials, and (5) thresholds of meaning. Results were summarized in a Summary of Measurement Properties (SOMP) table for each instrument. OMERACT CTD-ILD Working Group members discussed and voted on the strength of evidence supporting these two instruments and voted to endorse, provisionally endorse, or not endorse either instrument. Results Forty Patient Research Partners reported these two measures are feasible (are not an unnecessary burden or represent an infeasible longitudinal assessment of their disease). A majority of the 18 CTD-ILD Working Group members voted that both the FVC and DLco are feasible and have face and content validity. The systematic literature review returned 1,447 non-duplicated articles, of which 177 met eligibility for full text review. Forty-eight studies (13 RCTs, 35 LOSs) were included in the qualitative analysis. The FVC SOMP table revealed high quality, consistent data with evidence of good performance for all five measurement properties, suggesting requisite published evidence to proceed with endorsement. The DLco SOMP table showed a lack of data to support test-retest reliability and inadequate evidence to support clinical trial discrimination. There was unanimous agreement (15 [100%]) among voting CTD-ILD Working Group members to endorse the FVC as an instrument for lung physiology in RCTs and LOSs in SSc-ILD. Based on currently available evidence, DLco did not meet the OMERACT criteria and is not recommended for use in RCTs to represent lung physiology of SSc-ILD. The OMERACT Technical Advisory Group agreed with these decisions. Conclusion The OMERACT Filter 2.1 was successfully applied to the domain of lung physiology in patients with SSc-ILD. The FVC was endorsed for use in RCTs and LOSs based on the Working Group's vote; DLco was not endorsed.

People with cystic fibrosis (pwCF) have experienced increased survival and wellbeing in recent decades, such that more than half of those living with CF are adults. Consequently, sexual and reproductive health is increasingly important for pwCF, because many are considering parenthood. Most men and some women with CF (wwCF) will have reduced fertility, which in both sexes is multifactorial. However, unplanned pregnancies in women are not rare, and contraception and its interaction with CF complications need to be addressed by the CF team. Reduced fertility may be overcome in most pwCF through use of assisted reproductive technologies; however, the risk of having offspring with CF must be considered. Most wwCF will have normal pregnancies, but premature birth is common, especially in the setting of reduced lung function and CF-related diabetes (CFRD); optimization of treatment is recommended during pregnancy planning. Parenting imposes an increased burden on pwCF, with the challenges of caring for the newborn, postpartum physiologic changes, and maintaining CF treatments. Most drugs used to treat CF are considered safe in pregnancy and lactation, but exceptions need to be acknowledged, including the limited data regarding safety of CF transmembrane conductance regulator (CFTR) modulators during conception, pregnancy, and lactation. Because most pwCF are eligible for highly effective CFTR modulators, fertility, contraception, and pregnancy in people with CF is changing. Prospective studies regarding these issues in people treated with CFTR modulators are paramount to provide evidence-based guidance for management in the current era of CF care.

Background Pulmonary hypertension is a heterogeneous disease, and a significant portion of patients at risk for it have CT imaging available. Advanced automated processing techniques could be leveraged for early detection, screening, and development of quantitative phenotypes. Pruning and vascular tortuosity have been previously described in pulmonary arterial hypertension (PAH), but the extent of these phenomena in arterial vs venous pulmonary vasculature and in exercise pulmonary hypertension (ePH) have not been described. Research Question What are the arterial and venous manifestations of pruning and vascular tortuosity using CT imaging in PAH, and do they also occur in ePH? Study Design and Methods A cohort of patients with PAH and ePH and control subjects with available CT angiograms were retrospectively identified to examine the differential arterial and venous presence of pruning and tortuosity in patients with precapillary pulmonary hypertension not confounded by lung or thromboembolic disease. The pulmonary vasculature was reconstructed, and an artificial intelligence method was used to separate arteries and veins and to compute arterial and venous vascular volumes and tortuosity. Results A total of 42 patients with PAH, 12 patients with ePH, and 37 control subjects were identified. There was relatively lower (median [interquartile range]) arterial small vessel volume in subjects with PAH (PAH 14.7 [11.7-16.5; P < .0001]) vs control subjects (16.9 [15.6-19.2]) and venous small vessel volume in subjects with PAH and ePH (PAH 8.0 [6.5-9.6; P < .0001]; ePH, 7.8 [7.5-11.4; P = .004]) vs control subjects (11.5 [10.6-12.2]). Higher large arterial volume, however, was only observed in the pulmonary arteries (PAH 17.1 [13.6-23.4; P < .0001] vs control subjects 11.4 [8.1-15.4]). Similarly, tortuosity was higher in the pulmonary arteries in the PAH group (PAH 3.5 [3.3-3.6; P = .0002] vs control 3.2 [3.2-3.3]). Interpretation Lower small distal pulmonary vascular volume, higher proximal arterial volume, and higher arterial tortuosity were observed in PAH. These can be quantified by using automated techniques from clinically acquired CT scans of patients with ePH and resting PAH., Graphical Abstract

Pulmonary function testing (PFT) is an important component of the evaluation, monitoring, and management of patients with suspected or established lung disease. Spirometry is easily accomplished in the primary care office setting; determination of lung volumes and diffusion capacity is performed in a pulmonary laboratory. Spirometry evaluates vital capacity of the lungs and expiratory flow rates and provides both numeric data and a graphic depiction of respiratory air flow. Characteristic patterns in spirometry-derived data allow the clinician to identify potential lung disease, as well as establish relative reversibility of airflow abnormalities.

A 17-year-old previously healthy Taiwanese girl presented with syncope on a background of 1 month of weakness, polyarthritis, and heliotrope rash. Her presentation and investigations, which included an elevated creatine phosphokinase level and diffuse myositis on lower limb MRI, were consistent with juvenile dermatomyositis (JDM).

Case Presentation A 24-year-old woman, a baby-sitter with no known comorbidities, presented to the outpatient department with complaints of modified Medical Research Council grade IV breathlessness for 3 months, chest pain, and dry cough for 2 weeks. There was no known disease history, including respiratory, flu-like illness, or connective tissue disorder. There was no use of chemotherapeutic, oral contraceptive drugs, exposure to toxic substances, or smoking. A review of systems was negative for fever, arthralgia, myalgia, Raynaud phenomenon, skin thickening, rash, or leg swelling. The patient had no family history suggestive of a genetic syndrome.

Background Glutathione S-transferase omega-1 (GSTO1-1) is a cytosolic enzyme that modulates the S-thiolation status of intracellular factors involved in cancer cell survival or in the inflammatory response. Studies focusing on chronic obstructive pulmonary disease (COPD) have demonstrated that GSTO1-1 is detectable in alveolar macrophages, airway epithelium and in the extracellular compartment, where its functions have not been completely understood. Moreover GSTO1-1 polymorphisms have been associated with an increased risk to develop COPD. Against this background, the aim of this study was to evaluate GSTO1-1 levels and its polymorphisms in cystic fibrosis (CF) patients. Methods Clinical samples from a previous study published by our groups were analyzed for GSTO1-1 levels and polymorphisms. For comparison, a model of lung inflammation in CFTR-knock out mice was also used. Results Our data document that soluble GSTO1-1 can be found in the airways of CF patients and correlates with inflammatory parameters such as neutrophilic elastase and the chemokine IL-8. A negative correlation was found between GSTO1-1 levels and the spirometric parameter FEV1 and the FEV1/FVC ratio. Additionally, the A140D polymorphism of GSTO1-1 was associated with lower levels of the antiinflammatory mediators PGE2 and 15(S)-HETE, and with lower values of the FEV1/FVC ratio in CF subjects with the homozygous CFTR ΔF508 mutation. Conclusions Our data suggest that extracellular GSTO1-1 and its polymorphysms could have a biological and clinical significance in CF. Pathophysiological functions of GSTOs are far from being completely understood, and more studies are required to understand the role(s) of extracellular GSTO1-1 in inflamed tissues.

The bronchodilatory effect of hydro-ethanolic extract of Z. multiflora was examined in asthmatic patients.Pulmonary function tests (PFTs) were measured before and 15, 30, 60, 90, 120, 150, and 180 min after administration of the extract (20 mg/kg) in 18 asthmatics and after theophylline syrup (6 mg/kg) in 12 patients.The extract of Z. multiflora significantly increased all PFT values, 30 to 180 min post-administration similar to the effect of theophylline (all, p0.001). Increased PFT values due to the extract were significantly declined 180 min but the effects of theophylline were declined 150 min after administration (p0.05 to p0.001). Values of PFTs at baseline, 30 and 180 min after drugs administration were not singnificantly different between the extract and theophylline.Z. multiflora showed a bronchodilatory effect in asthmatic patients comparable to theophylline effect but with a longer duration of action.

BACKGROUND: Cystic fibrosis (CF) is characterized by neutrophilic inflammation in the airways. Leukotriene B4 (LTB4) is a neutrophil chemoattractant and has been implicated in CF pathogenesis. Acebilustat, a novel, synthetic, small-molecule leukotriene A4 hydrolase inhibitor, reduces LTB4 production. We report findings from a randomized placebo-controlled trial of acebilustat in adult subjects with mild-to-moderate lung disease.METHODS: Subjects were randomized (1:1:1) to once-daily acebilustat 50 mg, 100 mg or placebo for 48 weeks, concomitantly with their current therapeutic regimen. Subjects were stratified by use of concomitant CF transmembrane conductance regulator (CFTR) modulators, baseline percent predicted forced expiratory volume in 1 second (ppFEV1) 50-75 and >75, and number of pulmonary exacerbations in the past year (1 or >1). Primary endpoints were the change from baseline in ppFEV1 and safety. Secondary endpoints included the rate of pulmonary exacerbations.RESULTS: Overall, 199 subjects were randomized and dosed (acebilustat 50 mg, n=67; acebilustat 100 mg, n=66; placebo, n=66). Baseline demographics and disease profile were well balanced among treatment groups. Acebilustat had no statistically significant effect on the primary endpoint of change in ppFEV1 at week 48 or the secondary endpoint pulmonary exacerbations. There was a trend towards reduced pulmonary exacerbations in subjects receiving acebilustat in pre-specified populations with ppFEV1>75 (35% rate reduction) and those on concomitant CFTR modulator therapy (20% rate reduction). Acebilustat was well tolerated.CONCLUSIONS: Acebilustat did not improve lung function. A trend towards reduced pulmonary exacerbations in subjects with an earlier stage of lung disease suggests a potential effect in this population.

Characterization of aerosol generation during exercise can inform the development of safety recommendations in the face of COVID-19.Does exercise at various intensities produce aerosols in significant quantities?In this experimental study, subjects were eight healthy volunteers (six men, two women) who were 20 to 63 years old. The 20-minute test protocol of 5 minutes rest, four 3-minute stages of exercise at 25%, 50%, 75%, and 100% of age-predicted heart rate reserve, and 3 minutes active recovery was performed in a clean, controlled environment. Aerosols were measured by four particle counters that were place to surround the subject.Age averaged 41 ± 14 years. Peak heart rate was 173 ± 17 beat/min (97% predicted); peak maximal oxygen uptake was 33.9 ± 7.5 mL/kg/min; and peak respiratory exchange ratio was 1.22 ± 0.10. Maximal ventilation averaged 120 ± 23 L/min, while cumulative ventilation reached 990 ± 192 L. Concentrations increased exponentially from start to 20 minutes (geometric mean ± geometric SD particles/liter): Fluke0.3 μm = 66 ± 1.8 → 1605 ± 3.8; 0.3-1.0 μm = 35 ± 2.2 → 1095 ± 4.6; Fluke 1.0-5.0 μm = 21 ± 2.0 → 358 ± 2.3; P-Trak anterior = 637 ± 2.3 → 5148 ± 3.0; P-Trak side = 708 ± 2.7 → 6844 ± 2.7; P-Track back = 519 ± 3.1 → 5853 ± 2.8. All increases were significant at a probability value of .05. Exercise at or above 50% of predicted heart rate reserve showed statistically significant increases in aerosol concentration.Our data suggest exercise testing is an aerosol-generating procedure and, by extension, other activities that involve exercise intensities at or above 50% of predicted heart rate reserve. Results can guide recommendations for safety of exercise testing and other indoor exercise activities.

Introduction Respiratory muscle oxygen consumption increases with the work of breathing. We hypothesized that reducing excessive respiratory muscle activity during exercise may improve exercise tolerance. Method We developed a device to provide real-time visual feedback of thoracoabdominal movement and used it to examine the influence of visual feedback of thoracoabdominal movement during diaphragmatic breathing on oxygen consumption in eight healthy men. While sitting on a wheelchair with the backrest reclined at 60 degrees, oxygen consumption per body weight (VO 2 /BW), minute ventilation (VE), tidal volume (VT), and breathing frequency (fR) were measured, breath-by-breath, using an expired-gas analyzer. The breathing pattern was analyzed by inductance plethysmography, with transducer bands over the chest and abdomen recording thoracoabdominal movements. Results There was no significant difference in RatioTH-ABD and the ventilatory parameters between diaphragmatic breathing and diaphragmatic breathing with visual feedback. The average VO 2 /BW during diaphragmatic breathing with visual feedback was 0.6 ml/kg lower than that during diaphragmatic breathing without visual feedback (p= Conclusion When visual feedback was used during diaphragmatic breathing, the RatioTH-ABD remained essentially unchanged, but VO2/BW decreased significantly. This suggests that visual feedback of thoracoabdominal movement during diaphragmatic breathing may reduce respiratory muscle oxygen consumption.

Airway dysbiosis has been associated with lung disease severity in patients with cystic fibrosis (CF). However, the relationship between dysbiosis, airway inflammation and lung function impairement remains poorly understood. The aim of this study was therefore to determine how the structure of the sputum microbiota, airway inflammation markers and spirometry are related in patients with CF. Sputum samples were collected from 106 CF patients between 12 and 72 years. These were analyzed by 16S rRNA gene amplicon sequencing. Moreover, levels of pro-inflammatory cytokines (IL-1β, IL-8, IL-6 and TNF-α) and Neutrophil elastase (NE) were determined. The relationship between the microbiota, inflammation markers and forced expiratory volume in one second percent predicted (FEV1% predicted) was evaluated by multi-parameter analysis. The microbiota α-diversity correlated inverse with inflammation markers IL-1β, IL-8, TNF-α, NE and positively with FEV1% predicted. Patients could be divided into 7 clusters based on their microbiota structure. The most diverse cluster was defined by oropharyngeal-like flora (OF) while the others were characterized by the dominance of a single pathogen. Patients with the diverse OF microbiota cluster had lower sputum inflammatory markers and higher FEV1% predicted compared to patients with a pathogen-dominated microbiota including Pseudomonas aeruginosa. Our results suggest that the diversity of the airway microbiota is an important biomarker of the severity of airway inflammation linking dysbiosis to lung function decline in patients with CF.

Summary Background & aims Bronchiectasis is a heterogeneous, chronic respiratory condition, in which the role of nutrition remains unclear and nutritional guidance is lacking. Few studies have explored the role of nutrition in disease management, and little is known about nutritional requirements during periods of stability or metabolic stress. The aim of this study was to characterise nutritional status and intakes in a cohort of patients and identify potential associations with body composition and functional capacity. Methods A prospective observational cohort study was undertaken in an adult population (>17 years). Bronchiectasis was confirmed by high-resolution computerised tomography (HRCT). Anthropometric (weight, height, Body Mass Index (BMI), triceps skinfold thickness (TSF), mid upper-arm circumference (MUAC) and mid arm muscle circumference (MAMC)] lung function and nutritional intakes were measured. Results were analysed as a whole and by disease aetiology [primary ciliary dyskinesia (PCD), Idiopathic cause (IC), bronchiectasis in association with asthma and other] and associations tested. Results In total, 128 participants (65.5% female) completed the study. Median handgrip strength (HGS) in the total sample was only 66.5% (IQR 60.5–89.8) of reference population norms and was low for those with PCD [58.0% (IQR 43.5–70.0))]. Univariate regression indicated that BMI was a statistically significant predictor of lung function in the whole population with HGS and weight identified as statistically significant predictors of lung function in PCD. The total population and each sub-group failed to meet estimated average requirements for energy but exceeded the Reference nutrient intake (RNI) for protein. Vitamin D was consistently Conclusion BMI lay within normal to overweight ranges within the whole population and sub-groups, but masked important functional, body composition and nutritional deficits. This was particularly so within a younger sub-group with PCD, who had impaired muscle function, when compared to other causal and associative diseases.

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Background Non-invasive ventilation (NIV) is an established treatment option for cystic fibrosis (CF) patients with type 2 respiratory failure but the benefits of this therapy remain unclear. This study examined the long-term outcomes and response to NIV in a large adult CF cohort. Methods All patients attending a UK adult CF Centre receiving NIV as treatment for hypercapnic respiratory failure over a nine-year period were studied prospectively. Detailed clinical data was recorded and longitudinal data measurements were examined for the three years pre and post NIV initiation to assess effect of this intervention. Results 94 patients, mean age 29.9 (SD 9.7) years, percent predicted FEV1 21.5 (7.3), received NIV. All patients commenced NIV in a hospital setting. 21 remain alive, 24 received double lung transplant, 49 died without lung transplantation. NIV use was associated with a stabilisation and improvement in both FEV1 and FVC from NIV set up to three years post follow-up, in addition to an increase in body mass index and attenuation of PCO2 (all p Conclusions NIV use in CF adults is associated with improvements in lung function and attenuation of hypercapnia which is maintained for up to three years post NIV initiation. Outcomes for CF patients with severe pulmonary disease commenced on NIV have significantly improved with fifty percent of patients expected to survive for approximately five years.

Background In 1992, a landmark study demonstrated clinical deterioration in respiratory function and nutritional status prior to the onset of cystic fibrosis-related diabetes (CFRD). We re-evaluated this outcome. Methods The Montreal Cystic Fibrosis Cohort is a prospective CFRD screening study. We performed a 6-year retrospective analysis of nutritional parameters and FEV1 (%) in subjects who developed incident CFRD and in controls who maintained normoglycemia (NG). In the former group, data was collected over 6 years prior to diabetes onset. Results Subjects (n = 86) had a mean age of 31.7 ± 8.1 years, BMI of 23.0 ± 4.0 kg/m2, and FEV1% of 70.1 ± 24.2%. Eighty-one percent had pancreatic insufficiency (PI). Patients were grouped as follows: NG+PS (pancreatic sufficient) (n = 16), NG+PI (pancreatic insufficient) (n = 21), CFRD+PS (n = 3) and CFRD+PI (n = 46). At their most recent screen NG+PS subjects had significantly greater BMI, as compared to NG+PI and CFRD+PI groups (26.2 ± 3.6 kg/m2 vs 22.6 ± 4.2 kg/m2 vs 22.1 ± 3.5 kg/m2, p = 0.0016). FEV1 was significantly greater in the NG+PS group (91.5 ± 16.8% vs 67.8 ± 25.3% vs 63.5 ± 22.2%, p = 0.0002). The rates of change in weight, BMI, fat mass (%), and FEV1 prior to the most recent visit (NG+PS, NG+PI groups) or to the diagnosis of de novo CFRD were similar between groups. Conclusion In a contemporary context, CFRD onset is not preceded by deterioration in BMI, fat mass, or pulmonary function. Low BMI and FEV1 are more closely associated with PI than a pre-diabetic state.

Background A small proportion of patients with chronic obstructive pulmonary disease (COPD) patients present severe pulmonary hypertension (PH), defined by mean pulmonary artery pressure (mPAP) ≥35 mm Hg measured by right heart catheterization. Little is known about the characteristics of severe PH-COPD. The aim of the study based on a national registry was to describe this phenotype. Methods We prospectively included and followed patients with incident PH-COPD. Clinical, functional, hemodynamic data at inclusion and follow-up were retrieved. Survival assessed by Kaplan-Meier analysis was the primary end-point. Results From 2012 to 2016, 99 patients from 13 French centers were included in the study (82 males; median age 66.0 years [interquartile range 62.0-72.0]). At inclusion, most patients had marked dyspnea (55.6% and 22.2% New York Heart Association class III and IV, respectively). During 12 months before inclusion, 42.9% had an exacerbation requiring a hospitalization. Pulmonary function tests showed a moderate obstructive pattern with median (interquartile range) FEV1 50.0 [35.0-63.0] % predicted and low diffusing capacity for carbon monoxide, median 20.0 [16.5-30.6] % predicted. The median values for PaO2 and PaCO2 on room air were 50.0 [44.8-62.0] and 36.0 [31.1-43.0] mm Hg. Median values of mPAP, pulmonary artery occlusion pressure, cardiac index and pulmonary vascular resistance were 42.0 [37.0-48.0] mm Hg, 11.0 [9.0-14.0] mm Hg, 3.0 [2.4-3.6] L/min/m2, and 6.3 [4.2-7.9] WU, respectively. Mean restricted survival was 15.0 [13.9-16.0] months. Conclusions Severe PH-COPD is characterized by moderate airway obstruction but marked dyspnea and marked hypoxemia, low DLCO and high mPAP. This phenotype is associated with poor prognosis.

Background There is conflicting evidence regarding the presence of limb muscle impairments in adults with cystic fibrosis (CF), and the factors associated with these muscle impairments. The objectives of this study were to compare limb muscle size and function between adults with CF and healthy controls; and to examine their associations with demographic and clinical variables in adults with CF. Methods The systematic review was performed using PRISMA guidelines. Studies were included if they measured any aspect of limb muscle size or function in adults with CF. Meta-analyses were performed to compare muscle variables between CF and healthy controls; and to examine their associations with demographic and clinical variables. Results Twenty-eight studies were included, with 747 adults with CF. The meta-analyses showed that adults with CF have smaller thigh muscles [standardized mean difference (SMD) = 0.57, p Conclusions Leg muscle atrophy and lower handgrip strength were noted. There may be a subgroup of adults with CF with knee extensor (quadriceps) weakness. Future studies are needed to better understand muscle impairments in people with CF; to explore the factors that can predict these muscle impairments; and to investigate their clinical significance in people with CF.

Summary Background Infection is a key component of bronchiectasis pathophysiology. Characterisation of the microbiome offers a higher degree of sensitivity and resolution than does traditional culture methods. We aimed to evaluate the role of the microbiome in determining the risk of exacerbation and long-term outcomes, including all-cause mortality, in bronchiectasis. Methods We did a prospective observational cohort study of patients with bronchiectasis from eastern Scotland. Patients were enrolled from Sept 11, 2012, to Dec 21, 2015, and followed until Jan 8, 2019, for long-term outcomes. Patients were included if they were aged 18 years or older, and had a high-resolution CT-confirmed diagnosis of bronchiectasis and clinical symptoms consistent with the disease. Sputum samples were obtained when patients were clinically stable. Repeat sputum samples were taken at stable and exacerbation visits during follow-up. The V3–V4 region of the bacterial 16S rRNA gene was sequenced using the Illumina MiSeq platform. The dominant bacterial genus in each sample was assigned on the basis of a previously published method. Microbiome characteristics were analysed for their association with measures of clinical disease severity and long-term outcomes using PERMANOVA, random forest, and survival analyses. Findings Sequencing data were obtained from the sputum samples of 281 patients with bronchiectasis who were included in the stable baseline cohort. 49 (17%) of 281 patients provided more than one sample when clinically stable and were included in the longitudinal analysis. 64 (23%) patients provided both stable and exacerbation samples. In both stable bronchiectasis and during exacerbations, a sputum microbiome dominated by Proteobacteria and Firmicutes was observed. Individual patients' microbiome profiles were relatively stable over time, during exacerbations and at disease stability. Lower microbiome diversity, measured using the Shannon-Wiener diversity index, was associated with more severe bronchiectasis defined by the bronchiectasis severity index, lower FEV1, and more severe symptoms. Random forest analysis of baseline samples identified Pseudomonas, Enterobacteriaceae, and Stenotrophomonas as being associated with severe bronchiectasis (bronchiectasis severity index ≥9) and greater lung inflammation and Pseudomonas and Enterobacteriaceae with more frequent exacerbations. Patients in whom Pseudomonas was dominant (n=35) were at increased risk of all-cause mortality (hazard ratio 3·12, 95% CI 1·33–7·36; p=0·0091) and had more frequent exacerbations (incident rate ratio 1·69, 95% CI 1·07–2·67; p=0·024) during follow-up compared with patients with other dominant genera (n=246). Interpretation A reduction in microbiome diversity, particularly one associated with dominance of Pseudomonas, is associated with greater disease severity, higher frequency and severity of exacerbations, and higher risk of mortality. The microbiome might therefore identify subgroups of patients at increased risk of poor outcomes who could benefit from precision treatment strategies. Further research is required to identify the mechanisms of reduced microbiome diversity and to establish whether the microbiome can be therapeutically targeted. Funding British Lung Foundation and European Respiratory Society EMBARC2 consortium.

Objective To investigate whether the decrease in dyspnea in neuromuscular diseases after air stacking (AS) occurs mostly in patients with decreased inspiratory muscle force and ensuing chest wall restriction or heterogeneous ventilation across the lungs. Design Interventional, before-after study. Setting A neurorehabilitation inpatient and outpatient center. Participants Fifteen consecutive adult patients affected by neuromuscular diseases (N=15). Interventions AS treatment. Main Outcome Measures Patients had vital capacity (VC) and sniff nasal inspiratory pressure (SNIP) measured. We measured Borg score, oxygen saturation, and ventilation heterogeneity across the lung as estimated from the difference between respiratory resistance at 5 and 19 Hz (R5-19) with the forced oscillation technique before and 5, 30, 60, and 120 minutes after applying AS. Results Before AS, Borg score was significantly related to R5-19 (r2 0.46, P Conclusions These findings suggest that dyspnea in neuromuscular diseases is related to heterogeneous ventilation rather than inspiratory muscle force and/or lung volumes decrease. Restoring ventilation distribution across the lungs with AS appears to improve dyspnea.

Rationale Poor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality. Methods At baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65 ± 8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48–119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality. Results PsD was lower in COPD patients than in controls (40.5 vs 42.5, p = 0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV1%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02–1.12, p = 0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94–0.99, p = 0.023) were the variables independently associated with all-cause mortality. Conclusions In COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.

Pulmonary function testing remains the central determinant of candidacy for pulmonary resection and indicator of perioperative risk. For patients with borderline pulmonary function, exercise testing can help determine surgical candidacy either via stair climbing or by obtaining a maximum oxygen consumption. The Thoracic Revised Cardiac Risk Index should be used to select patients for further cardiac testing. Patient comorbidities, medications, functional limitations, and smoking status are also requisite assessments of the preoperative evaluation that influence perioperative outcomes. A minimally invasive approach to pulmonary resection reduces perioperative risk and may be of most benefit to patients with borderline pulmonary function.

Coronary artery bypass grafting (CABG) often causes physiological changes in patients. Although functional changes, such as lung function and exercise capacity changes, are observed in patients, there are no detailed studies examining this. The aim was to compare preoperative and postoperative pulmonary function and exercise capacity in patients undergoing on-pump CABG with a multidimensional index (BODE index). Demographic and surgical characteristics of patients were recorded. Pulmonary function test, six-minute walk test (6MWT), and modified Medical Research Council (mMRC) dyspnea score were assessed and BODE index were calculated in preoperative and at six months postoperatively. A total of 75 patients were included with a mean ± standard deviation age of 59.8±10.0 years. The male to female ratio was 57/18. There was a statistically significant decrease in the forced expiratory flow at 25-75% (FEF25-75%) value after CABG. Other pulmonary function test values were also lower in the postoperative period compared to the preoperative period, but these changes were not significant. The mean distance achieved in the 6MWT (p=0.02) and the mMRC dyspnea score (p=0.001) were significantly better postoperatively. The BODE index, which combines these parameters, had increased in the postoperative period. Age (OR 1.09; 95% CI: 1.008-1.181) and postoperative FEF25-75% (OR -0.96; 95% CI: 0.938-0.988) were the independent predictors of BODE score ≥3 in multivariate analysis. Despite the decrease in pulmonary function in patients undergoing CABG, there was an improvement in exercise capacity and dyspnea score.

Case Presentation A 75-year-old woman was referred to the pulmonary office in January 2020 for cough and progressive worsening of shortness of breath over the years. Her medical history was significant for asthma that was diagnosed approximately 10 years earlier, when she first developed dyspnea. A pre-bronchodilator spirometry at that time showed severe airflow obstruction ( Fig 1 ). The patient was incidentally found to have several noncalcified pulmonary nodules on a chest CT scan in 2015, which was obtained as a part of dyspnea workup. She underwent bronchoscopic evaluation with transbronchial biopsy of the largest nodule (1.6 × 1.2 cm) in the right middle lobe. She was diagnosed with low-grade neuroendocrine tumor (typical carcinoid) and had been under surveillance without any progression in the number of nodules or the size of the existing nodules. She was a lifelong nonsmoker and no family history of asthma. Over the years, she received multiple courses of systemic corticosteroids and different inhalers, without any improvement in her symptoms. The patient was frustrated by the lack of perceived benefit, and she discontinued all respiratory medications. She denied any fever, night sweats, exertional chest pain, or seasonal allergies but reported cough, wheezing, and severe exertional shortness of breath. She was unable to walk more than 20 feet at a time. She had no pets at home and did not travel outside the United States. Her only home medications were multivitamins and low-dose aspirin.

Background The importance of exercise in the management of people with CF is well recognised, yet the effect of exercise on lung function is not well understood. FEV1 is insensitive to the detection of small changes in lung function. Ventilation MRI and LCI are both more sensitive to mild lung disease than FEV1 and may be better suited to assess the effects of exercise. Here we assessed the short-term effects of maximal exercise on the distribution of ventilation using ventilation MRI and LCI. Methods Patients with CF and a range of lung disease were assessed. Baseline LCI and ventilation MRI was followed by a maximal cardio-pulmonary exercise test (CPET). Repeated ventilation MRI was performed within 30 minutes of exercise termination, followed by LCI and finally by FEV1. Results 13 patients were recruited and completed all assessments. Mean (SD) age was 25 (10) years and mean (SD) FEV1 z-score was -1.8 (1.7). Mean LCI at baseline was 8.2, mean ventilation defect percentage on MRI (VDP) was 7.3%. All patients performed maximal CPET. Post-exercise, there was a visible change in lung ventilation in 85% of patients, including two patients with increased ventilation heterogeneity post-CPET who had normal FEV1. VDP and LCI were significantly reduced post-exercise (p Conclusions Acute maximal exercise directly affects the distribution of ventilation on ventilation MRI in patients with CF. This suggests that exercise is beneficial in CF and that ventilation MRI is suitable to assess airway clearance efficacy.

Background Recurrent or unresolved wheezing is a common complaint in certain young children populations, especially those born preterm. Using infant lung function testing, we aimed to distinguish the differences between term and preterm young children with recurrent wheezing. Materials and Methods Children under 2 years of corrected age were enrolled if they had 3 or more wheezing episodes during the enrollment period. Healthy term controls of comparable age were also recruited for reference. Measurements of lung function were made, including tidal breathing, passive respiratory mechanics, and forced tidal and raised-volume expiration. For children with recurrent wheezing, raised-volume forced expiration was repeated after an adequate delivery of bronchodilator nebulization was achieved. Results In total, 68 young children (40 with recurrent wheezing and 28 healthy controls) were recruited. Among children with recurrent wheezing, 23 preterm children (preterm group), and 17 term children (term group) were enrolled. Compared with healthy controls, both the term and preterm groups had lower lung function as measured by absolute values and z scores. The term group performed worse than the preterm group with regard to forced vital capacity, forced expiratory volume at 0.5 s (FEV0.5), and peak expiratory flow. Following bronchodilator nebulization, the term group had significantly higher increases in FEV0.5 and forced mid-expiratory flow than the preterm group. Conclusion Young children with recurrent wheezing, especially term infants, demonstrated lower lung function than healthy controls. Moreover, the term group evidenced greater responsiveness to bronchodilators than the preterm group. The distinct bronchodilator responses may offer further information to guide the diagnosis and treatment of young children with recurrent wheezing.

Background This study explored the safety and feasibility of uniportal video-assisted thoracoscopic (VATS) decortication in patients presenting with stage III tuberculous empyema with severe rib crowding. Methods From August 2017 to January /2019, 33 patients with stage III tuberculous empyema and severe rib crowding underwent uniportal VATS decortication with partial rib resection and the use of a customized periosteal stripper. Preoperative and postoperative chest computed tomography (CT) imaging and pulmonary function testing were analyzed to evaluate the clinical significance of certain imaging findings and surgical efficacy. Results There was 1 conversion to open thoracotomy. Median operative time was 3.5 hours (range, 2.1-4.5 hours) and the median blood loss was 500 mL (range, 250-1000 mL). There were no perioperative mortalities. The incidence of prolonged air leaks (>5 days) was 81.8%. Median postoperative hospital stay was 4 days (range, 4-5 days). All patients were discharged with 2 chest tubes, and median duration drainage was 39 days (range, 30-60 days). The presence of a low-density line between the parietal fibrous pleural rind and chest wall was demonstrated on chest CT in 13 patients. Intraoperative blood loss was considerably lower in these patients compared with those without this imaging finding. Follow-up was complete in all patients over a median of 8 months (range, 6-11.5 months). All patients recovered well and achieved notable improvement in pulmonary function. Conclusions Uniportal VATS decortication is safe and effective. Patients presenting with a low-density line around the thickened fibrous pleural rind on preoperative chest CT scan may be good candidates.

Case Presentation A 44-year-old woman with a history of renal cell carcinoma and thyroid cancer was referred to our institution for evaluation of cystic lung disease. She was an active smoker with a 15-pack-year of tobacco use. Two years before her presentation, she underwent a left nephrectomy for renal cell carcinoma, clear cell type. Four months before, she had a total thyroidectomy that showed nodules consistent with noninvasive follicular thyroid neoplasm with papillary like nuclear features. She had no previous pulmonary complaints. Her family history was positive for breast cancer in her grandmother. There was no family history of pneumothorax. She complained of mild shortness of breath with exertion and occasional nonproductive cough. As part of her oncologic work up, she underwent a chest CT scan of the lungs ( Fig 1 ).

Background: Many microRNAs (miRNAs) have been associated with asthma and chronic obstructive pulmonary disease (COPD). Longitudinal lung function growth trajectories of children with asthma—normal growth, reduced growth (RG), early decline (ED), and RG with an ED (RGED)—have been observed, with RG and RGED associated with adverse outcomes, including COPD. Objective: Our aim was to determine whether circulating miRNAs from an early age in children with asthma would be prognostic of reduced lung function growth patterns over the next 16 years. Methods: We performed small RNA sequencing on sera from 492 children aged 5 to 12 years with mild-to-moderate asthma from the CAMP clinical trial, who were subsequently followed for 12 to 16 years. miRNAs were assessed for differential expression between previously assigned lung function growth patterns. Results: We had 448 samples and 259 miRNAs for differential analysis. In a comparison of the normal and the most severe group (ie, normal growth compared with RGED), we found 1 strongly dysregulated miRNA, hsa-miR-145-5p (P < 8.01E–05). This miR was downregulated in both ED groups (ie, ED and RGED). We verified that miR-145-5p was strongly associated with airway smooth muscle cell growth in vitro. Conclusion: Our results showed that miR-145-5p is associated with the ED patterns of lung function growth leading to COPD in children with asthma and additionally increases airway smooth muscle cell proliferation. This represents a significant extension of our understanding of the role of miR-145-5p in COPD and suggests that reduced expression of miR-145-5p is a risk factor for ED of long-term lung function., GRAPHICAL ABSTRACT