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ObjectiveT cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsIn this 12-month, randomized, double-blind, placebo-controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets.ResultsAmong 88 participants, the adjusted mean change in the MRSS at 12 months was -6.24 units for those receiving abatacept and -4.49 units for those receiving placebo, with an adjusted mean treatment difference of -1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal-like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively.ConclusionIn this phase II trial, abatacept was well-tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

ObjectiveTo investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD).MethodsPatients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm.ResultsBaseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only).ConclusionIn a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.

Rationale: A positive bronchodilator response (BDR) according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines require both 200 ml and 12% increase in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after bronchodilator inhalation. This dual criterion is insensitive in those with high or low FEV1.Objectives: To establish BDR criteria with volume or percentage FEV1 change.Methods: The largest FEV1 and FVC were identified from three pre- and three post-bronchodilator maneuvers in COPDGene (Genetic Epidemiology of COPD) participants. A total of 7,741 individuals with coefficient of variation less than 15% for both FEV1 and FVC formed bronchodilator categories of FEV1 response: negative (≤0.00% or ≤0.00 L), minimal (>0.00% to ≤9.00% or >0.00 L to ≤0.09 L), mild (>9.00% to ≤16.00% or >0.09 L to ≤0.16 L), moderate (>16.00% to ≤26.00% or >0.16 L to ≤0.26 L), and marked (>26.00% or >0.26 L). These response size categories are based on empirical limits considering average FEV1 increase of approximately 160 ml and the clinically important difference for FEV1. To compare flow and volume response characteristics, BDR-FEV1 category assignments were applied for the BDR-FVC response.Results: Twenty percent met mild and 31% met moderate or marked BDR-FEV1 criteria, whereas 12% met mild and 33% met moderate or marked BDR-FVC criteria. In contrast, only 20.6% met ATS/ERS positive criteria. Compared with the negative BDR-FEV1 category, the minimal, mild, moderate, and marked BDR-FEV1 categories were associated with greater 6-minute-walk distance and lower St. George's Respiratory Questionnaire and modified Medical Research Council dyspnea scale scores. Compared with negative BDR, moderate and marked BDR-FEV1 categories were associated with fewer exacerbations, and minimal BDR was associated with lower computed tomography airway wall thickness. Compared with the negative category, all BDR-FVC categories were associated with increasing emphysema percentage and gas trapping percentage. Moderate and marked BDR-FVC categories were associated with higher St. George's Respiratory Questionnaire scores but fewer exacerbations and lower dyspnea scores.Conclusions: BDR grading by FEV1 volume or percentage response identified subjects otherwise missed by ATS/ERS criteria. BDR grades were associated with functional exercise performance, quality of life, exacerbation frequency, dyspnea, and radiological airway measures. BDR grades in FEV1 and FVC indicate different clinical and radiological characteristics.

BackgroundSmoking is a major risk factor for COPD and may impact the efficacy of COPD treatments; however, a large proportion of COPD patients continue to smoke following diagnosis.MethodsThis post-hoc analysis of pooled data from the replicate 12-week, placebo-controlled GEM1 and GEM2 studies assessed the impact of smoking status on the efficacy and safety of glycopyrrolate 15.6 μg twice daily vs placebo in patients with moderate-to-severe COPD. Data from 867 patients enrolled in GEM1 and GEM2 were pooled for analysis and grouped by smoking status (57% current smokers, 43% ex-smokers). Forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 12 h, trough FEV1, forced vital capacity, St George's Respiratory Questionnaire (SGRQ) total score, COPD assessment test (CAT) score, transition dyspnea index (TDI) focal score, daily symptom scores, and rescue medication use were assessed in current smokers and ex-smokers. Incidences of adverse events (AEs) and serious AEs (SAEs) were also assessed.ResultsTreatment with glycopyrrolate resulted in significant improvements in all lung function measures, independent of smoking status. In both current and ex-smokers, changes from baseline in trough FEV1 were less marked in patients taking inhaled corticosteroids (ICS) than those not receiving ICS. Changes from baseline in SGRQ total score and rescue medication use were significantly greater with glycopyrrolate compared with placebo, regardless of smoking status. Changes in the CAT score, TDI focal score, and daily symptom scores significantly improved versus placebo, but only in current smokers. Improvements in patient-reported outcomes (PROs) with glycopyrrolate relative to placebo were numerically greater in current smokers than ex-smokers. The incidences of AEs and SAEs were similar regardless of smoking status.ConclusionsIn this post-hoc analysis of GEM1 and GEM2, glycopyrrolate use led to significant improvements in lung function, independent of baseline smoking status; improvements were less marked among patients receiving background ICS, regardless of baseline smoking status. Improvements in PROs were greater with glycopyrrolate than placebo, and the magnitude of changes was numerically greater among current smokers. The safety profile of glycopyrrolate was comparable between current smokers and ex-smokers.

Abstract Background Although Osteogenesis Imperfecta (OI) affects the connective tissue, pulmonary function might be compromised because of thoracic deformities. OI is known to be a restrictive lung disease, but spirometry provides global measurement without localizing the site of the restriction. Opto-electronic plethysmography (OEP), is a non-invasive method able to underline altered respiratory function as well as ventilatory thoraco-abdominal paradoxes during spontaneous breathing. We aimed to reconstruct the thoraco-abdominal surface, to perform local analyses of trunk motion and to make quantitative comparison of trunk shape and respiratory kinematics according to OI severity, particularly during maximal inspiratory and expiratory expansions. This is a cross-sectional study where we have studied the thoraco-abdominal compartmental analysis in 26 adult OI patients (14 Type III) at rest and during vital capacity manoeuvre using OEP. We have also applied a new method that created realistic and accurate 3D models to perform local analyses of trunk motion and to make quantitative comparison of trunk shape and respiratory kinematics. Results Type III patients were characterized by lower spirometric lung volume, by lower sleep quality, by a more compressed thoracic configuration aggravated by severe scoliosis, by reduced global expansion at rest and during maximal maneuvers because of the reduced expansion of the pulmonary ribcage at rest (12% vs. 65% in healthy subjects), during maximal inspiration (37% vs. 69%) and expiration (16% vs. 68%) with local paradoxical movement occurring on the side of the ribcage region. Conclusion The kinematics of the trunk changed to compensate for the severe structural deformities by shifting the expansion in the abdomen both at rest and during maximal manoeuvre because of a restricted thorax. For the first time, we have quantified and localized the site of the restriction in OI patients in the lateral part of the thorax. The 3D analysis proposed seemed a promising graphical immediate new method for pathophysiology study of chest wall restriction.

Objective To assess associations between the extent of fibrotic interstitial lung disease (ILD) and forced vital capacity (FVC) at baseline and change in FVC over 52 weeks in patients with systemic sclerosis-associated ILD (SSc-ILD) in the SENSCIS trial. Material and methods We used generalized additive models, which involve few assumptions and allow for interaction between non-linear effects, to assess associations between the extent of fibrotic ILD on high-resolution computed tomography (HRCT), and the interplay of extent of fibrotic ILD on HRCT and FVC % predicted, at baseline and FVC decline over 52 weeks. Results In the placebo group (n  = 288), there was weak evidence of a modest association between a greater extent of fibrotic ILD at baseline and a greater decline in FVC % predicted at week 52 [r: –0.09 (95% CI –0.2, 0.03)]. Higher values of both the extent of fibrotic ILD and FVC % predicted at baseline tended to be associated with greater decline in FVC % predicted at week 52. In the nintedanib group (n  = 288), there was no evidence of an association between the extent of fibrotic ILD at baseline and decline in FVC % predicted at week 52 [r: 0.01 (95% CI: -0.11, 0.12)] or between the interplay of extent of fibrotic ILD and FVC % predicted at baseline and decline in FVC % predicted at week 52. Conclusions Data from the SENSCIS trial suggest that patients with SSc-ILD are at risk of ILD progression and benefit from nintedanib largely irrespective of their extent of fibrotic ILD at baseline. Study registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT02597933. [ABSTRACT FROM AUTHOR]

Background: Preoxygenation during anesthesia can be done by 3 min tidal volume breath and eight vital capacity breath in 1 min, conventionally. Population of our country is not homogenous. Aims and Objectives: The present study was conducted to validate preoxygenation processes in people of eastern India. Materials and Methods: Total 140 patients of ASA grade I and II, age group 20–50 posted for surgeries under GA were allotted in TV and VC group. Every odd number and even number patient was tested for TV method and VC method, respectively, with a Magill circuit and airtight face mask with 100% oxygen flow at a rate of 10 L/min. Time and number of breaths were noted when end tidal oxygen concentration ≥90% in TV and VC group, respectively. Results: In TV method, the mean time (in minute) was 3.10±0.27 and 3.13±0.24 for tribal and non-tribal sub-group (P=0.80); 3.02±0.37 and 3.10±0.27 for tribal and non-tribal male (P=0.57); and 3.18±0.05 and 3.16±0.21 for tribal and non-tribal female (P=0.57). In VC method, mean number of VC breaths was 8.32±0.60 and 8.43±0.74 for tribal and non-tribal subgroup (P=0.76); 8.75±0.49 and 8.23±0.70 for tribal and non-tribal male (P=0.42); and 8.20±0.60 and 8.60±0.72 for tribal and non-tribal female (P=0.16). Patients completing preoxygenation in TV and VC method – tribal: 22% and 53%, non-tribal: 4% and 62%, tribal male: 22% and 20%, non-tribal male: 8% and 68%, tribal female: 0% and 60%, and nontribal female: 0 and 57%, respectively. Conclusion: No significant difference found between tribal and non-tribal groups of both sexes in each method. Completion of preoxygenation was higher in VC group, though not tested statistically. [ABSTRACT FROM AUTHOR]

Objective: The effects of preoperative respiratory muscle training (RMT) on postoperative complications in patients surgically treated for myasthenia gravis (MG) remain unclear. The present study therefore evaluated the effects of preoperative moderate-to-intense RMT and aerobic exercise, when added to respiratory physiotherapy, on respiratory vital capacity, exercise capacity, and duration of hospital stay in patients with MG. Methods: Eighty patients with MG scheduled for extended thymectomy were randomly divided into two groups. The 40 subjects in the study group (SG) received preoperative moderate-to-intense RMT and aerobic exercise in addition to respiratory physiotherapy, whereas the 40 subjects in the control group (CG) received only chest physiotherapy. Respiratory vital capacity (as determined by VC, FVC, FEV1, FEV1/FVC, and PEF) and exercise capacity (as determined by the 6-min walk test [6 MWT]) were measured pre- and postoperatively and before discharge. The duration of hospital stay and activity of daily living (ADL) were also determined. Results: Demographic and surgical characteristics, along with preoperative vital capacity and exercise capacity, were similar in the two groups. In the CG, VC (p = 0.001), FVC (p = 0.001), FEV1 (p = 0.002), PEF (p = 0.004), and 6MWT (p = 0.041) were significantly lower postoperatively than preoperatively, whereas the FEV1/FVC ratio did not differ significantly. Postoperative VC (p = 0.012), FVC (p = 0.030), FEV1 (p = 0.014), and PEF (p = 0.035) were significantly higher in the SG than in the CG, although 6MWT results did not differ. ADL on postoperative day 5 was significantly higher in the SG than in the CG (p = 0.001). Conclusion: RMT and aerobic exercise can have positive effects on postoperative respiratory vital capacity and daily life activity, and would enhance recovery after surgery in MG patients. [ABSTRACT FROM AUTHOR]

Problem Statement and Purpose: Soccer is a sport characterized by high intensity and duration. The energy needed to play a soccer match is provided by aerobic metabolism. Therefore, it is important to determine such parameters as oxygen consumption and maximal oxygen consumption in soccer players. The aim of the study is to track the changes in the functional indicators of professional soccer players during the spring half-season and to give recommendations for changes in the training plan to increase their performance and reduce fatigue at the end of the season. Approach: The study involved 13 professional soccer players and was conducted in the period January - June. Functional examination of respiration - spirometry and determination of gas exchange parameters during exercise - spiroergometry were performed twice at the beginning and at the end of the period. Results: The spirometry data of the subjects showed values close to the predicted values. The decrease in values at the end of the spring half-season is probably due to the fatigue accumulated during this period. Although the values show a decrease in the parameters, there is no statistically significant difference in the two measurements of the Tifno index, but there is a statistically significant difference in the decrease in VC (Wilcoxon signed rank test, p value = 0.04) and FEO1 (Wilcoxon signed rank test, p value = 0.0002). The fact that even the indicators at the beginning of the study are to some extent underestimated, shows the accumulation of fatigue in the players and the need to rethink the overall training plan with corresponding individual approaches to each soccer player in order to optimize the training-recovery ratio. There was a slight increase (statistically insignificant) in mean VO2max and VO2max/kg during the spring half-season, indicating that training resulted in an increase in aerobic capacity. This is an indication that conditioning training is producing the desired result and can be carried out without any major changes. Conclusions: The benefit of periodic medical and functional examinations of football players is mainly in two directions. First, it provides information about the current state of health of the athlete under study and his fitness to participate in training and sports competitions. And, secondly, it enables the coach, analyzing the results, to assess the specific functional capabilities of the football players, to make changes in the training schedule and specific exercises, to pay attention to recovery and to apply an individual approach to each specific case in order to improve specific indicators. [ABSTRACT FROM AUTHOR]

Study Design: Systematic review and meta-analysis Objectives: This study's objective is to provide a critical review of the current literature regarding the changes in pulmonary function (PF) in Adolescent idiopathic scoliosis (AIS) patients who have undergone posterior spinal fusion and instrumentation (PSF), with and without thoracoplasty (TP). Methods: A comprehensive search was performed using the following databases: EMBASE, PubMed, EBSCOhost (CINAHL and Medline) and OpenGrey. Our focus was on studies that compared pre-and postoperative percent-predicted values of forced vital capacity (%FVC) or forced expiratory volume in 1 second (%FEV1) in AIS patients who had undergone PSF, with and without TP, with a minimum 2-year follow-up. The risk of bias for included studies was assessed using the ROBINS-I ("Risk Of Bias In Non-randomised Studies - of Interventions") tool. Mean change scores were depicted using forest plots. Results: Fifteen studies met our inclusion criteria. The results of our analysis suggest that PSF with TP caused a significant deterioration of %FVC in individuals with moderate AIS, with no significant effect on %FEV1. It also showed a minor improvement of FEV1% in individuals with moderate AIS after PSF only, but no significant change in %FVC. Conclusions: PSF with TP caused a significant deterioration of % FVC while PSF alone caused a minor improvement of FEV1% in individuals with moderate AIS with a minimum 2-year follow-up. [ABSTRACT FROM AUTHOR]

Depression is a severe and common mental disorder. The association between depressive symptoms and lung function remains unclear. To determine whether depressive symptoms are associated with lung function in U.S. adults without pulmonary diseases. A cross-sectional study of National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2012 were used to estimate the relationship between depressive symptoms and lung function. Depressive symptoms were determined by a participant's score on the Patient Health Questionnaire-9. Forced Expiratory Volume 1st Second (FEV1) Forced Vital Capacity (FVC) were determined by the spirometry. Weighted multivariate linear regression was used to analyze this relationship and subgroup analyses were performed. Of 8027 participants, 576 (7.18 %) participants with depression. Depression group had significant lower FEV1 and FVC than non-depression group. After adjustment for all covariates, there was a significant negative association between depressive symptoms and FVC (β −4.84, 95 % CI −9.10 to −0.57), especially in non-Hispanic White people (β −9.03, 95 % CI −14.38 to −3.69). There was no independent association between depressive symptoms and FEV1 in all participants, whereas the association was significant in non-Hispanic White people (β −4.91, 95 % CI −9.50 to −0.32). High depressive symptoms were independently associated with decline of FVC among U.S. adults without pulmonary diseases, especially in non-Hispanic White people. In addition, although it was not independently associated with FEV1 in all participants, depressive symptom score was also negatively associated with FEV1 in non-Hispanic White people. • High depressive symptoms were independently associated with decline of FVC among U.S. adults without pulmonary diseases. • High depressive symptoms were more obvious associated with decline of FVC in non-Hispanic White people. • High depressive symptoms were also independently associated with decline of FEV1 in non-Hispanic White people. [ABSTRACT FROM AUTHOR]

BackgroundNon-communicable lung disease and exposure to air pollution are major problems in sub-Saharan Africa. A high burden of chronic respiratory symptoms, spirometric abnormalities and air pollution exposures has been found in Malawian adults; whether the same would be true in children is unknown.MethodsThis cross-sectional study of children aged 6-8 years, in rural Malawi, included households from communities participating in the Cooking and Pneumonia Study (CAPS), a trial of cleaner-burning biomass-fuelled cookstoves. We assessed; chronic respiratory symptoms, anthropometry, spirometric abnormalities (using Global Lung Initiative equations) and personal carbon monoxide (CO) exposure. Prevalence estimates were calculated, and multivariable analyses were done.ResultsWe recruited 804 children (mean age 7.1 years, 51.9% female), including 476 (260 intervention; 216 control) from CAPS households. Chronic respiratory symptoms (mainly cough (8.0%) and wheeze (7.1%)) were reported by 16.6% of children. Average height-for-age and weight-for-age z-scores were -1.04 and -1.10, respectively. Spirometric abnormalities (7.1% low forced vital capacity (FVC); 6.3% obstruction) were seen in 13.0% of children. Maximum CO exposure and carboxyhaemoglobin levels (COHb) exceeded WHO guidelines in 50.1% and 68.5% of children, respectively. Children from CAPS intervention households had lower COHb (median 3.50% vs 4.85%, p=0.006) and higher FVC z-scores (-0.22 vs -0.44, p=0.05) than controls.ConclusionThe substantial burden of chronic respiratory symptoms, abnormal spirometry and air pollution exposures in children in rural Malawi is concerning; effective prevention and control strategies are needed. Our finding of potential benefit in CAPS intervention households calls for further research into clean-air interventions to maximise healthy lung development in children.

ObjectiveTo compare safety and efficacy outcomes between the cyclophosphamide (CYC) arms of Scleroderma Lung Study (SLS) I and II.MethodsParticipants enrolled in the CYC arms of SLS I (n = 79) and II (n = 69) were included. SLS I and II randomized participants to oral CYC for 1 year and followed patients for an additional year off therapy (in SLS II, patients received placebo in Year 2). Eligibility criteria for SLS I and II were nearly identical. Outcomes included the forced vital capacity (FVC%)-predicted and DLCO%-predicted (measured every 3 mos) and quantitative radiographic extent of interstitial lung disease (measured at 1 and 2 yrs for SLS I and SLS II, respectively). Joint models were created to evaluate the treatment effect on the course of the FVC/DLCO over 2 years while controlling for baseline disease severity.ResultsSLS I and II CYC participants had similar baseline characteristics. After adjusting for baseline disease severity, there was no difference in the course of the FVC%-predicted (p = 0.535) nor the DLCO%-predicted (p = 0.172) between the SLS I and II CYC arms. In both groups, treatment with CYC led to a significant improvement in the FVC%-predicted from 3 to 12 months, but no significant improvement beyond this point. Treatment with CYC had no effect on the DLCO for either group.ConclusionTreatment with 1 year of oral CYC led to similar improvements in lung function in both SLS I and II, although the effects were not sustained following cessation of CYC. These results suggest that increasing the duration of ILD therapy may improve outcomes for patients with systemic sclerosis-ILD.

Spirometry is the current gold standard for diagnosing and monitoring the progression of Chronic Obstructive Pulmonary Disease (COPD). However, many current and former smokers who do not meet established spirometric criteria for the diagnosis of this disease have symptoms and clinical courses similar to those with diagnosed COPD. Large longitudinal observational studies following individuals at risk of developing COPD offer us additional insight into spirometric patterns of disease development and progression. Analysis of forced expiratory maneuver changes over time may allow us to better understand early changes predictive of progressive disease. This review discusses the theoretical ability of spirometry to capture fine pathophysiologic changes in early airway disease, highlights the shortcomings of current diagnostic criteria, and reviews existing evidence for spirometric measures which may be used to better detect early airflow impairment.

BackgroundHispanic subjects with cystic fibrosis (CF) have increased morbidity and mortality than non-Hispanic white subjects. The ethnic disparity in mortality varies by region. Factors influencing pulmonary function vary by both ethnicity and region.ObjectiveTo determine if the ethnic difference in pulmonary function varies by region.MethodsThis retrospective cohort study compared differences in longitudinal pulmonary function (percent-predicted forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1 ], forced expiratory flow at 25% to 75% [FEF25-75 ], FEV1 /FVC, and FEV1 decline) between Hispanic and non-Hispanic white subjects with CF by Census region of the United States (West, South, Midwest, and Northeast). Subjects were of ages 6 to 25 years and in the CF Foundation Patient Registry from 2008 to 2013. We used linear mixed effects models with subject-specific slopes and intercepts, adjusting for 14 demographic and clinical variables.ResultsOf 14 932 subjects, 1433 (9.6%) were Hispanic and 13 499 (90.4%) were non-Hispanic white. Hispanic subjects' FEV1 was 9.0% (8.3%-9.8%) lower than non-Hispanic white subjects in the West, while Hispanic subjects' FEV1 was only 4.0% (3.0%-5.0%) lower in the Midwest, 4.4% (3.1%-5.7%) lower in the Northeast, and 4.4% (3.2%-5.5%) lower in the South. Similarly, FVC and FEF25-75 were lower among Hispanic subjects compared to non-Hispanic white subjects in all US regions, with the biggest differences in the West. Only in the West was FEV1 /FVC significantly lower in Hispanic subjects (-0.019; -0.022 to -0.015). FEV1 decline was not significantly different between ethnicities in any region.ConclusionsIn CF, Hispanic subjects have lower pulmonary function than non-Hispanic white subjects in all geographic regions with the largest difference in occurring in the West.

Rationale: The American Thoracic Society (ATS)/European Respiratory Society defines a positive bronchodilator response (BDR) by a composite of BDR in either forced expiratory volume in 1 second (FEV1) and/or forced vital capacity (FVC) greater than or equal to 12% and 200 ml (ATS-BDR). We hypothesized that ATS-BDR components would be differentially associated with important chronic obstructive pulmonary disease (COPD) outcomes. Objectives: To examine whether ATS-BDR components are differentially associated with clinical, functional, and radiographic features in COPD. Methods: We included subjects with COPD enrolled in the COPDGene study. In the main analysis, we excluded subjects with self-reported asthma. We categorized BDR into the following: 1) No-BDR, no BDR in either FEV1 or FVC; 2) FEV1-BDR, BDR in FEV1 but no BDR in FVC; 3) FVC-BDR, BDR in FVC but no BDR in FEV1; and 4) Combined-BDR, BDR in both FEV1 and FVC. We constructed multivariable logistic, linear, zero-inflated negative binomial, and Cox hazards models to examine the association of BDR categories with symptoms, computed tomography findings, change in FEV1 over time, respiratory exacerbations, and mortality. We also created models using the ATS BDR definition (ATS-BDR) as the main independent variable. Results: Of 3,340 COPD subjects included in the analysis, 1,083 (32.43%) had ATS-BDR, 182 (5.45%) had FEV1-BDR, 522 (15.63%) had FVC-BDR, and 379 (11.34%) had Combined-BDR. All BDR categories were associated with FEV1 decline compared with No-BDR. Compared with No-BDR, both ATS-BDR and Combined-BDR were associated with higher functional residual capacity %predicted, greater internal perimeter of 10 mm, and greater 6-minute-walk distance. In contrast to ATS-BDR, Combined-BDR was independently associated with less emphysema (adjusted beta regression coefficient, -1.67; 95% confidence interval [CI], -2.68 to -0.65; P = 0.001), more frequent respiratory exacerbations (incidence rate ratio, 1.25; 95% CI, 1.03-1.50; P = 0.02) and severe exacerbations (incidence rate ratio, 1.34; 95% CI, 1.05-1.71; P = 0.02), and lower mortality (adjusted hazards ratio, 0.76; 95% CI, 0.58-0.99; P = 0.046). Sensitivity analysis that included subjects with self-reported history of asthma showed similar findings. Conclusions: BDR in both FEV1 and FVC indicates a COPD phenotype with asthma-like characteristics, and provides clinically more meaningful information than current definitions of BDR.

BACKGROUND: Duchenne muscular dystrophy (DMD) patients experience skeletal muscle degeneration, including respiratory muscles. Respiratory decline in glucocorticoid-treated DMD patients, measured by percent predicted forced vital capacity (FVC% p), is typically 5% annually in patients aged 10 to 18 years. OBJECTIVE: Evaluate the effects of eteplirsen on FVC% p annual change in 3 trials versus matched Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) controls. METHODS: Eteplirsen studies 201/202 evaluated eligible ambulatory DMD patients for at least 4 years, study 204 evaluated primarily non-ambulatory DMD patients for 2 years, and ongoing study 301 is evaluating ambulatory DMD patients for 2 years (interim analysis is included). Eteplirsen-treated patients (n = 74) were amenable to exon 51 skipping and were receiving glucocorticoids. Three CINRG DNHS cohorts included: glucocorticoid-treated patients amenable to exon 51 skipping (Exon 51 CINRG DNHS; n = 20), all glucocorticoid-treated CINRG patients (All CINRG DNHS; n = 172), and all glucocorticoid-treated genotyped CINRG DNHS patients (Genotyped CINRG DNHS; n = 148). FVC% p assessments between ages 10 and

ObjectiveTo assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II.MethodsSLS I randomised 158 patients with SSc-ILD to 1  year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling.ResultsAfter a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data.ConclusionIn addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.

BackgroundAmbulatory function predicts morbidity and mortality and may be influenced by cardiopulmonary dysfunction. Persons living with HIV (PLWH) suffer from a high prevalence of cardiac and pulmonary comorbidities that may contribute to higher risk of ambulatory dysfunction as measured by 6-minute walk test distance (6-MWD). We investigated the effect of HIV on 6-MWD.MethodsPLWH and HIV-uninfected individuals were enrolled from 2 clinical centers and completed a 6-MWD, spirometry, diffusing capacity for carbon monoxide (DLCO) and St. George's Respiratory Questionnaire (SGRQ). Results of 6-MWD were compared between PLWH and uninfected individuals after adjusting for confounders. Multivariable linear regression analysis was used to determine predictors of 6-MWD.ResultsMean 6-MWD in PLWH was 431 meters versus 462 in 130 HIV-uninfected individuals (p = 0.0001). Older age, lower forced expiratory volume (FEV1)% or lower forced vital capacity (FVC)%, and smoking were significant predictors of decreased 6-MWD in PLWH, but not HIV-uninfected individuals. Lower DLCO% and higher SGRQ were associated with lower 6-MWD in both groups. In a combined model, HIV status remained an independent predictor of decreased 6-MWD (Mean difference = -19.9 meters, p = 0.005).ConclusionsHIV infection was associated with decreased ambulatory function. Airflow limitation and impaired diffusion capacity can partially explain this effect. Subjective assessments of respiratory symptoms may identify individuals at risk for impaired physical function who may benefit from early intervention.

ObjectiveBronchodilator responsiveness (BDR) is prevalent in COPD, but its clinical implications remain unclear. We explored the significance of BDR, defined by post-bronchodilator change in FEV1 (BDRFEV1) as a measure reflecting the change in flow and in FVC (BDRFVC) reflecting the change in volume.MethodsWe analyzed 2974 participants from a multicenter observational study designed to identify varying COPD phenotypes (SPIROMICS). We evaluated the association of BDR with baseline clinical characteristics, rate of prospective exacerbations and mortality using negative binomial regression and Cox proportional hazards models.ResultsA majority of COPD participants exhibited BDR (52.7%). BDRFEV1 occurred more often in earlier stages of COPD, while BDRFVC occurred more frequently in more advanced disease. When defined by increases in either FEV1 or FVC, BDR was associated with a self-reported history of asthma, but not with blood eosinophil counts. BDRFVC was more prevalent in subjects with greater emphysema and small airway disease on CT. In a univariate analysis, BDRFVC was associated with increased exacerbations and mortality, although no significance was found in a model adjusted for post-bronchodilator FEV1.ConclusionWith advanced airflow obstruction in COPD, BDRFVC is more prevalent in comparison to BDRFEV1 and correlates with the extent of emphysema and degree of small airway disease. Since these associations appear to be related to the impairment of FEV1, BDRFVC itself does not define a distinct phenotype nor can it be more predictive of outcomes, but it can offer additional insights into the pathophysiologic mechanism in advanced COPD.Clinical trials registrationClinicalTrials.gov: NCT01969344T4.

Abstract Background The forced vital capacity (FVC) of healthy individuals depends on their age, sex, ethnicity and height. Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by loss of FVC. We compared FVC values in the subjects with SSc-ILD in the SENSCIS trial of nintedanib versus placebo with values from hypothetical matched healthy references. Methods The SENSCIS trial enrolled subjects with SSc with first non-Raynaud symptom in the prior ≤ 7 years, extent of fibrotic ILD on HRCT ≥ 10%, and FVC ≥ 40% predicted. FVC at baseline and decline in FVC over 52 weeks were compared with FVC values in hypothetical healthy reference subjects matched 1:1 to the subjects in the trial for age, sex, ethnicity and height, determined using equations published by the European Respiratory Society Global Lung Function Initiative. Results At baseline, mean (SD) FVC was 2460 (737) mL in the nintedanib group (n = 287) compared with 3403 (787) mL in the hypothetical matched healthy references. Mean (SD) FVC was 2544 (817) mL in the placebo group (n = 286) compared with 3516 (887) mL in the hypothetical matched healthy references. Mean (SE) changes in FVC at week 52, i.e., age-related loss of lung function, in the hypothetical healthy references matched to the nintedanib and placebo groups, respectively, were − 26.3 (0.5) mL and − 25.8 (0.5) mL. The difference in the change in FVC at week 52 between the nintedanib group and the hypothetical healthy references was 26.6 mL (95% CI: 1.2, 52.0; p = 0.04). The difference in the change in FVC at week 52 between the placebo group and the hypothetical healthy references was 77.5 mL (95% CI: 51.4, 103.7; p

Abstract Background Even almost 30 years after the ban on the use of asbestos in Germany, the effects of asbestos are still highly relevant in everyday clinical practice in occupational medicine. The aim of this study was to further investigate the significance of essential parameters of both pulmonary function diagnostics and imaging techniques (low-dose HR-TCT) for the prevention and early detection of asbestos-related morphological and functional lung changes. Methods Data from spirometry, body plethysmography and diffusion capacity, as well as CT images of the thorax, were retrospectively studied from 72 patients examined between 2017 and 2019 at the Institute for Occupational and Maritime Medicine (ZfAM), Hamburg, Germany. The subjects were divided into four subgroups according to the presence of comorbidities (concomitant cardiac diseases, obstructive ventilatory disorder, pulmonary function pattern consistent with emphysema, and no other pulmonary or cardiac diseases). These subgroups were analysed in addition to the overall collective. The CT images were evaluated according to the International Classification of Occupational and Environmental Respiratory Diseases (ICOERD) with radiological expertise. In addition, some asbestos-related parameters were newly quantified, and corresponding scores were defined based on ICOERD. Statistical analysis included the use of correlations and fourfold tables with calculation of Spearman's rho (ρ), Cohen’s κ, and accuracy. Results Vital capacity (VC) is slightly reduced in the total collective compared to the normal population (mean 92% of predicted value), while diffusion capacity for CO (DLCO) shows predominantly pathological values, mean 70% of the respective predicted value. The CO transfer coefficient (DLCO/VA), which refers to alveolar volume (VA), also shows slightly decreased values (mean 87% pred.). Seventy-nine percent of patients (n = 57) had signs of pulmonary fibrosis on CT scans, and pleural plaques appeared in 58 of 72 patients (81%). Of the newly quantified additional parameters, particularly frequently described findings are subpleural curvilinear lines (SC, n = 39) and parenchymal bands (PB, n = 29). VC correlates well with the expression of pleural plaques (ρ = − 0.273, P

Background and Study Aim. To assess the effects of Anulom Vilom Pranayama (AVP) or alternative nostril breathing and Rope Mallakhamb Training (RMT) on respiratory parameters among university females with athletic backgrounds. Material and Methods. A quasi experimental study was performed on thirty-six, university female students from the Department of Physical Education (T), Guru Nanak Dev University, Amritsar, Punjab, India. The subjects were divided in three groups. The groups were subjected to 4-weeks of intervention including: Group A (n1=12) subjected to AVP, Group B (n2=12) subjected to RMT, and Group C: (n3=12) no training or control. Respiratory parameters were measured twice, pre and post intervention using a wet spirometer. All measurements were performed three times and the average values were recorded for analysis. Results. 4-weeks of AVP resulted in positive increases for respiratory parameters measured including Tidal Volume (VT) 25.7%, Inspiratory Reserve Volume (IRV) 29.4%, Expiratory Reserve Volume (ERV) 27.1%, Vital Capacity (VC) 33.2%, and Inspiratory Capacity (IC) 31.6% compared to the control group. Also, 4-weeks of RMT had a positive impact on respiratory parameters including (VT) 19.8%, (IRV) 22%, (ERV) 19.4%, (VC) 32 % and (IC) 28.1% compared to the control group. Conclusions. Both AVP and RMT had a positive impact on respiratory parameters. Also, AVP training has a more positive impact on respiratory parameters than RMT and may also contribute to the enhancement of concentration-based performance and voluntary control of breathing among young females from athletic backgrounds. As a result, AVP training can be more beneficial for a competitive edge in order to improve the athletes' primary need for respiratory endurance.

BACKGROUND:Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established. METHODS:We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used the Sobel test to determine whether markers of systemic inflammation mediated a link between spirometric and radiographic features of COPD and CAC. RESULTS:FEV1/FVC but not quantitative emphysema or airway wall thickening was associated with CAC (p = 0.036), after adjustment for demographics, diabetes mellitus, hypertension, statin use, and CT scanner type. To explain this discordance, we examined visual subtypes of emphysema and airway disease, and found that centrilobular emphysema but not paraseptal emphysema or bronchial thickening was independently associated with CAC (p = 0.019). MMP3, VCAM1, CXCL5 and CXCL9 mediated 8, 8, 7 and 16% of the association between FEV1/FVC and CAC, respectively. Similar biomarkers partially mediated the association between centrilobular emphysema and CAC. CONCLUSIONS:The association between airflow obstruction and coronary calcification is driven primarily by the centrilobular subtype of emphysema, and is linked through bioactive molecules implicated in the pathogenesis of atherosclerosis. TRIAL REGISTRATION:ClinicalTrials.gov: Identifier: NCT01969344 .

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1 ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV1 which do not follow the expected trends of the normal population. We also show that "normalization" of FVC and FEV1 using general population data to generate percent predicted values underestimates the pulmonary involvement in OI. Within each subtype of OI, we used linear mixed models to find potential correlations between FEV1 and FVC with the clinical variables including mobility, bisphosphonate use, and scoliosis. Our results are an important step in understanding the extent of pulmonary involvement in individuals with OI and for developing pulmonary endpoints for use in the routine patient care as well as in the investigation of new therapies.

The present study aimed to investigate the relationship between postural stability, external breathing, and sex, as this area of research is not yet well explored. The study included 19 healthy participants, both male and female, and compared their breathing parameters in three positions: sitting, standing, and supine. The objective was to collect data to develop a non-contact method for recording external respiration. The analysis included measurements of vital capacity and forced vital capacity pulmonary tests, as well as parameters of natural breathing. We confirmed that the lung volume component was higher in males than in females in the sitting position. Additionally, postural influence on breathing was observed only in male participants, with no significant impact on females. Men also exhibited an increased respiratory rate in both standing and supine positions, as well as increased minute ventilation when standing as compared to sitting. Furthermore, men demonstrated higher maximum inspiratory and expiratory vital capacities in all positions as compared to women. These results have important implications not only for the development of non-contact methods for recording respiration but also in the studies of vertical stance, in clinical investigations.

Copyright of Revista Brasileira de Medicina do Esporte is the property of Redprint Editora Ltda. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: This study aimed to examine the association between cardiopulmonary function, health-related quality of life (HRQOL) and cognitive function among nursing home residents aged 80 years and over. Methods: A nursing home-based, cross-sectional study was implemented among 677 aged over 80 years in Shanghai, China. A total of 197 participants underwent effective cardiopulmonary function examinations. Mini-Mental Status Examination (MMSE) and Short Form-36 scales (SF-36) were used to assess cognitive function and HRQOL, respectively. Results: Decline in left ventricular ejection fractions (LVEF) [adjusted odds ratio (AOR), 1.98; 95% confidential interval (CI), 1.03–3.81)] and vital capacity (VC) (AOR, 2.08; 95%CI, 1.07–4.04) was associated with cognitive impairment. After adjusting confounding factors, relationships between cognitive function and physical functioning (PF) (AOR, 0.98; 95%CI, 0.97–0.99) still existed. Conclusions: Healthcare professionals should pay more attention to cardiopulmonary health and HRQOL in the nursing home residents. Actions of public health strategies focus on the improvement of cardiopulmonary function, and PF among older nursing home residents with cognitive impairment is required. [ABSTRACT FROM AUTHOR]

Background and Purpose: Diminished pulmonary function is associated with negative health outcomes and pulmonary impairment, and can be associated with frailty. The objectives of this study were to compare pulmonary function between frail, prefrail, and nonfrail older adults; to verify the association between pulmonary function and frailty syndrome; and to establish cut-off points for pulmonary function variables for predicting frailty. Methods: A cross-sectional study was conducted with 379 community-dwelling older adults of both sexes. Spirometry was used to measure pulmonary function criteria (forced vital capacity, FVC; forced expiratory volume in 1 second, FEV1; and FEV1/FVC ratio). The presence of frailty was evaluated with Fried's frailty phenotype. Statistical analysis included a multinomial logistic regression model. Pulmonary function cut-off points for discriminating frailty syndrome were established through analysis of the receiver operating characteristic curves. Results and Discussion: The study participants were a median of 69.0 (64.0-74.0) years old, and 12.4% presented frailty while 58% presented prefrailty. Frail and prefrail older adults presented significantly lower median FVC and FEV1 values—FVC = 1.89 L (1.45-2.31) and FEV1 = 1.60 L (1.24-1.91); FVC = 2.07 L (1.62-2.67) and FEV1 = 1.66 L (1.32-2.09), respectively—than nonfrail participants—FVC = 2.53 L (1.96-3.16) and FEV1 = 2.01 L (1.54-2.43). The adjusted analysis indicated that FEV1 (odds ratio [OR] = 0.63; 95% confidence interval [CI], 0.39-0.99) and the FVC (OR = 0.68; 95% CI, 0.48-0.96) were inversely associated with prefrailty and that FVC (OR = 0.52; 95% CI, 0.29-0.94) was associated with frailty. Cut-off points for prefrailty (FVC ≤2.3 L and FEV1≤1.86 L) and frailty (FVC ≤2.07 L and FEV1≤1.76 L) were established. Conclusions: Pulmonary function was lower in frail and prefrail older adults than in their nonfrail peers. Frailty and prefrailty were inversely associated with pulmonary function. Cut-off points for FEV1 and FVC for discriminating frailty were established and may allow pulmonary function to serve as an indicator of frailty in older adults. [ABSTRACT FROM AUTHOR]

Copyright of Revista Brasileira de Medicina do Esporte is the property of Redprint Editora Ltda. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Evaluation of anthropometric characteristics and respiratory functions is imperative for investigating the health status of individuals and sportspersons. The objective of this study was to evaluate the anthropometric characteristics and respiratory function parameters of rugby and soccer players. Methods: Forty-four players (rugby, n=22; soccer, n=22) were selected for the present study. They were free of musculoskeletal and respiratory disorders. Their age was 21.49±1.41 years, height 173.62±6.26 cm, weight 71.40±14.44 kg, BMI 22.70±4.26 kg/m2, PBF 17.35±12.27%, Fat Mass 24.43±13.61 kg, and LBM 55.98±7.26 kg. Anthropometric characteristics and body composition were measured using a weighing scale cum stadiometer and a bioelectric impedance analyzer. Respiratory function was assessed using a handheld spirometer. Standard procedures were followed to measure the anthropometric characteristics, body composition, and respiratory function. Results: The results of the study demonstrated no significant differences in anthropometric characteristics and body composition between rugby and soccer players. The respiratory function parameters were insignificant for vital capacity (VC) (MWU=213, p=0.496), forced expiratory volume in the first second (FEV1) (MWU=216, p=-0.541), forced expiratory volume in the first second divided by vital capacity (FEV/VC) (MWU=205.5, p=0.390), and maximum voluntary ventilation (MVV) (MWU=224.5, p=0.681) among rugby and soccer players; only a significant difference was found in forced vital capacity (FVC) (MWU=142.5, p=0.019) in rugby and soccer players. Conclusion: Based on findings from the study, it can be concluded that rugby players have higher values for respiratory functions than soccer players. The findings of this study can inform future researchers, coaches, and team instructors regarding the preparation of rugby and soccer players for specific training and competitions. [ABSTRACT FROM AUTHOR]

Depth-based plethysmography (DPG) for the measurement of respiratory parameters is a mobile and cost-effective alternative to spirometry and body plethysmography. In addition, natural breathing can be measured without a mouthpiece, and breathing mechanics can be visualized. This paper aims at showing further improvements for DPG by analyzing recent developments regarding the individual components of a DPG measurement. Starting from the advantages and application scenarios, measurement scenarios and recording devices, selection algorithms and location of a region of interest (ROI) on the upper body, signal processing steps, models for error minimization with a reference measurement device, and final evaluation procedures are presented and discussed. It is shown that ROI selection has an impact on signal quality. Adaptive methods and dynamic referencing of body points to select the ROI can allow more accurate placement and thus lead to better signal quality. Multiple different ROIs can be used to assess breathing mechanics and distinguish patient groups. Signal acquisition can be performed quickly using arithmetic calculations and is not inferior to complex 3D reconstruction algorithms. It is shown that linear models provide a good approximation of the signal. However, further dependencies, such as personal characteristics, may lead to non-linear models in the future. Finally, it is pointed out to focus developments with respect to single-camera systems and to focus on independence from an individual calibration in the evaluation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Blatta orientalis is an indicated remedy for asthma and other chronic obstructive pulmonary diseases in homeopathic medicine. Preclinical studies indicate that B. orientalis shows anti-asthmatic properties in animals when induced with bronchospasm using acetylcholine through nonselective anticholinergic and antihistaminic activities. However, no studies have explored the changes in the vital capacity of the lungs on administering the homeopathic remedy, B. orientalis. It is shown that isometric contraction of pectoral muscles enhances the vital capacity of lungs by increasing ventilation and decreasing alveolar partial pressure of carbon dioxide. It can act as a valuable tool for monitoring the vital capacity of the lungs before and after administration of B. orientalis. AIM: This preliminary research takes the first step toward exploring vital capacity through a randomized, placebo-controlled study elucidating the effects of ongoing isometric contraction of muscles on the vital capacity of lungs of healthy individuals on the administration of B. orientalis in different potencies. It aims to compare changes in the vital capacity of lungs in healthy participants during an acute bout of isometric contraction by handgrip dynamometer after administration of B. orientalis. MATERIALS AND METHODS: Eighteen participants who fulfilled the inclusion criteria gave voluntary consent to participate in this research study. The research team measured the Tmax (measured by handgrip dynamometer) and the vital capacity (measured by a vitalograph) of these participants at the baseline. The participants were then placed into three-medicine arms to administer medicine orally: Arm 1 – B. orientalis Q, Arm 2 – B. orientalis 30C, and Arm 3 – placebo, following allocation of six participants in each medicine arm. Lottery method was used for grouping participants randomly to each medicine arm. The participants were numbered from 1 to 18 using the lottery method, and it was made sure that each arm had one male and five females to have similar gender distribution. The research team blindfolded the participants with a cloth bandage (dupatta) before categorizing them into different medicine arms. The team measured each participant's Tmax and vital capacity, and then administered one dose of the assigned medicine. The team measured the Tmax and vital capacity of the participants after 10 min of administering the medicine. The process was repeated after every 24 h for 3 consecutive days. RESULTS: The effect of ongoing isometric contractions of the skeletal muscles on the vital capacity acted as a great tool to measure improvement in vital capacity. The vital capacity of the lungs was significantly decreased after oral administration of B. orientalis Q and B. orientalis 30C, whereas there was no significant effect found in the arm that received a placebo. CONCLUSION: This preliminary study shows that B. orientalis decreases the vital capacity of lungs in healthy subjects and calls for further exploration of its action in higher potencies and with wider experimental parameters. Following the Law of Similimum, this inference also adds to the research scope on the potential of this homeopathic medicine in patients with restrictive lung diseases where the vital lung capacity gets significantly decreased.

Background: During pregnancy, women undergo adaptive changes in different organ systems including the respiratory system by hormonal changes and mechanical pressures. Several previous studies reported the change in pulmonary functions in pregnancy and tribal populations. However, trimester-wise, pulmonary functions in tribal women residing in Jharkhand, India, are not available. Aim: This study aimed to find and compare the pulmonary function test parameters in tribal and non-tribal women in singleton first, second, and third trimesters of pregnancy. Methods: We conducted this cross-sectional observational study in a tertiary care hospital in Jharkhand, India, with 58 tribal women and 116 age-matched controls. The pulmonary function tests, namely forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEFR), maximal mid expiratory flow (MMEF) were measured with a computerized spirometer (Spiro Excel, Medicaid, Punjab, India) and FEV1/FVC was calculated. Results: A total of 58 tribal women with median age 22 (Q1–Q3: 21–25) years and 116 non-tribal women with median age 22 (20–25) (P=0.33) participated in the study. The tribal women showed higher respiratory rate (20 [18–24.5] vs. 16 [15–18] per minute, P

Background and Aims: Preoxygenation is supplementation of 100% oxygen prior to induction of general anaesthesia to increase the body's oxygen stores. Efficacy of preoxygenation can be increased by optimising fresh gas flow (FGF) rate and pattern of breathing. Methods: Based on pattern of breathing—Tidal Volume Breathing (TVB) or Deep Breathing (DB) and FGF-10 L/min or 15 L/min—100 subjects of the American Society of Anesthesiologists physical status I/II posted for elective surgery were recruited and randomised into four groups: T10 - TVB with 10 L/min; D10 - DB with 10 L/min; T15 - TVB with 15 L/min; and D15 - DB with 15 L/min. A tight-fitting anaesthesia mask along with continuous positive airway pressure of 5 cm of H2O with 20° head-up was used for preoxygenation. The total time taken and the total number of breaths required to achieve end tidal oxygen concentration (EtO2) of 90% were noted. Exhaled tidal volume (Vte), end tidal carbon dioxide, fraction of inspired oxygen, and EtO2 were recorded at each breath. Analysis of variance (ANOVA) was used for inferential statistics and Tukey's honestly significant difference (HSD) test was used to calculate mean difference in total time and number of breaths amongst the groups. Results: Total time taken was significantly low (P < 0.001) in DB compared to TVB (D10: 70.2 ± 19.91, D15: 68.4 ± 20.27 vs T10: 112.28 ± 47.96, T15: 113.6 ± 48.57 seconds). Number of breaths was significantly high (P < 0.001) in TVB with 22.84 ± 8.73, 23.76 ± 11.64, 10.56 ± 3.69, and 8.32 ± 1.8 in T10, T15, D10 and D15, respectively. Vte was significantly low in TVB (P < 0.001). Conclusion: Rapid preoxygenation can be achieved by DB at high FGF of a minimum of 10 L/min.

Respiratory disorders may be one of the adverse effects of sedentary lifestyle. This study investigated respiratory functions (FEV1, FVC and PEFR) and anthropometric parameters (body weight and body mass index) of healthy young males and females participating in moderate aerobic exercise. Forty young healthy untrained non-athletes, twenty males and twenty females (age, 25 ± 5.6 years; body weight, 65 ± 4.0 kg; body height, 176.9 ± 2.5 cm) volunteered to participate in this study. The exercise regimen was of moderate intensity lasting for 20 min daily on a treadmill consistently at the speed of 13 km/h for 14 days. The weight and height of participants were measured using medical scale and wall-mounted stadiometer respectively. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were assessed using digital spirometer. The results showed a significant (p

The diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstration of airflow obstruction. Traditional spirometric indices miss a number of subjects with respiratory symptoms or structural lung disease on imaging. We hypothesized that utilizing all data points on the expiratory spirometry curves to assess their shape will improve detection of mild airflow obstruction and structural lung disease. We analyzed spirometry data of 8307 participants enrolled in the COPDGene study, and derived metrics of airflow obstruction based on the shape on the volume-time (Parameter D), and flow-volume curves (Transition Point and Transition Distance). We tested associations of these parameters with CT measures of lung disease, respiratory morbidity, and mortality using regression analyses. There were significant correlations between FEV1/FVC with Parameter D (r = -0.83; p

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P

BackgroundThe identification of smoking-related lung disease in current and former smokers with normal FEV1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV1/FVC between the LLN and 0.70 is heterogeneous, and aimed to characterize the burden of smoking-related lung disease in this group.MethodsWe compared spirometry, chest CT characteristics, and symptoms between 161 ever-smokers in the discordant group and 940 ever-smokers and 190 never-smokers with normal FEV1 and FEV1/FVC > 0.70 in the SPIROMICS cohort. We also estimated sensitivity and specificity for diagnosing objective radiographic evidence of chronic obstructive pulmonary disease (COPD) using different FEV1/FVC criteria thresholds.ResultsThe discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV1 and FEF25-75, and higher respiratory medication use compared with the other two groups. Within the discordant group, 44% had radiographic CT evidence of either emphysema or non-emphysematous gas trapping; an FEV1/FVC threshold of 0.70 has greater sensitivity but lower specificity compared with LLN for identifying individuals with CT abnormality.ConclusionsEver-smokers with normal FEV1 and FEV1/FVC  LLN are a heterogeneous group that includes significant numbers of individuals with and without radiographic evidence of smoking-related lung disease. These findings emphasize the limitations of diagnosing COPD based on spirometric criteria alone.

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

ObjectivesTo examine the relationship between residential proximity to agricultural fumigant use and respiratory symptoms and lung function in 7-year old children.MethodsParticipants were 294 children living in the agricultural Salinas Valley, California and enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study. We obtained information on respiratory symptoms and asthma medication use from maternal questionnaires and children performed spirometry to determine the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25-75% (FEF25-75) at 7-years of age. We estimated agricultural fumigant use within 3, 5 and 8 km of residences during pregnancy and from birth to age 7 using California's Pesticide Use Report data. We evaluated the association between prenatal and postnatal residential proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene with respiratory symptoms and use of asthma medication with logistic regression models and continuous lung function measurements with linear regression models adjusted for confounders.ResultsThere were no significant associations between residential proximity to use of fumigants and respiratory symptoms or use of asthma medication. We did not observe any adverse relationships between residential proximity to fumigant use and lung function measurements. Unexpectedly, we observed suggestive evidence of improved FEV1 and FEF25-75 with higher use of methyl bromide and chloropicrin during the prenatal period. For example, for each 10-fold increase in methyl bromide use during the prenatal development period we observed higher FEV1 (β = 0.06 L/s; 95% CI: 0.00, 0.12) and higher FEF25-75 (β = 0.15 L/s; 95% CI: 0.03, 0.27). Maternal report of child allergies (runny nose without a cold during the previous year) modified the relationship between FEV1 and prenatal proximity to methyl bromide use (p = .07) and we only observed higher FEV1 among children without allergies (β = 0.08 L/s; 95% CI: 0.02, 0.14 for a 10-fold increase in methyl bromide use during the prenatal period).ConclusionsResidential proximity to agricultural fumigant use during pregnancy and childhood did not adversely affect respiratory health in the children through 7 years of age. These findings should be explored in larger studies.

BackgroundIndividuals with metabolic syndrome (MetS) and diabetes (DM) are more likely to have decreased lung function and are at greater risk of cardiovascular disease (CVD).HypothesisLung-function measures can predict CVD events in older persons with MetS, DM, and neither condition.MethodsWe followed 4114 participants age ≥ 65 years with and without MetS or DM in the Cardiovascular Health Study. Cox regression examined the association of forced vital capacity (FVC) and 1-second forced expiratory volume (FEV1 ; percent of predicted values) with incident coronary heart disease and CVD events over 12.9 years.ResultsDM was present in 537 (13.1%) and MetS in 1277 (31.0%) participants. Comparing fourth vs first quartiles for FVC, risk of CVD events was 16% (HR: 0.84, 95% CI: 0.59-1.18), 23% (HR: 0.77, 95% CI: 0.60-0.99), and 30% (HR: 0.70, 95% CI: 0.58-0.84) lower in DM, MetS, and neither disease groups, respectively. For FEV1 , CVD risk was lower by 2% (HR: 0.98, 95% CI: 0.70-1.37), 26% (HR: 0.74, 95% CI: 0.59-0.93), and 31% (HR: 0.69, 95% CI: 0.57-0.82) in DM. Findings were strongest for predicting congestive heart failure (CHF) in all disease groups. C-statistics increased significantly with addition of FEV1 or FVC over risk factors for CVD and CHF among those with neither MetS nor DM.ConclusionsFEV1 and FVC are inversely related to CVD in older adults with and without MetS, but not DM (except for CHF); however, their value in incremental risk prediction beyond standard risk factors is limited mainly to metabolically healthier persons.

BackgroundIdiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF.MethodsWe identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 μg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates.ResultsOne hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each μg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008).ConclusionsAmbient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease.

ObjectivesTo assess the reliability and the minimal clinically important differences (MCID) for FVC% predicted in the Scleroderma Lung Study I and II.MethodsUsing data from SLS I and II (N=300), we evaluated the test-retest reliability for FVC% predicted (FVC%; screening vs. baseline) using intra-class correlation (ICC). MCID estimates at 12 months were calculated in the pooled cohort (SLS-I and II) using 2 anchors: Transition Dyspnea Index (≥change of 1.5 units for improvement and worsening, respectively) and the SF-36 Health Transition question: "Compared to one year ago, how would you rate your health in general now?", where "somewhat better" or "somewhat worse" were defined as the MCID estimates. We next assessed the association of MCID estimates for improvement and worsening of FVC% with patient reported outcomes (PROs) and computer-assisted quantitation of extent of fibrosis (QLF) and of total ILD (QILD) on HRCT.ResultsReliability of FVC%, assessed at a mean of 34 days, was 0.93 for the pooled cohort. The MCID estimates for the pooled cohort at 12 months for FVC% improvement ranged from 3.0 % to 5.3% and for worsening from -3.0% to -3.3%. FVC% improvement by ≥MCID was associated with either statistically significant or numerical improvements in some PROs, QILD, and QLF, while FVC% worsening ≥MCID was associated with statistically significant or numerical worsening of PROs, QILD, and QLF.ConclusionFVC% has acceptable test-retest reliability, and we have provided the MCID estimates for FVC% in SSc-ILD based changes at 12 months from baseline in two clinical trials. Clinical trial registration available at www.clinicaltrials.gov, IDs NCT00004563 and NCT00883129.

BACKGROUND:The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment. METHODS:The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients. RESULTS:A total of 404 patients received treatment, with 165 participating in the ESWT substudy. A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% ( p = 0.02)] but not with tiotropium/olodaterol 2.5/5 µg [9% ( p = 0.14)] versus placebo. In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 µg [21% ( p = 0.055)] and tiotropium/olodaterol 2.5/5 µg [21% ( p = 0.056)] versus placebo. CONCLUSION:Tiotropium/olodaterol 5/5 µg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time. [ ClinicalTrials.gov identifier: NCT01525615.].

BackgroundPreclinical studies have demonstrated that low-dose carbon monoxide (CO) can abrogate experimental lung fibrosis. To test the therapeutic role of inhaled CO, we designed a clinical study in patients with idiopathic pulmonary fibrosis (IPF).MethodsWe conducted a multicenter, phase IIa, double-blinded, sham-controlled, clinical trial. Patients with IPF were randomized to treatment with inhaled CO at 100 to 200 parts per million or to inhaled 21% oxygen for 2 h daily, twice weekly, for 12 weeks. The primary study end point was the difference in change in matrix metalloproteinase-7 (MMP7) serum concentration after 12 weeks of treatment. Secondary end points included pulmonary function test measures, 6-min walk distance, rates of adverse events, acute exacerbation, hospitalization and death, and quality of life measures.ResultsFifty-eight subjects were randomized to treatment with inhaled CO (n = 29) or placebo (n = 29). Despite modest increases in CO blood levels, the change in MMP7 concentrations after 12 weeks of treatment did not significantly differ between the study arms (MMP7 difference at week 12, -0.90 ng/mL; 95% CI, -4.18 to 2.38 ng/mL). No differences were observed in physiologic measures, incidence of acute exacerbations, hospitalization, death, or patient-reported outcomes. Importantly, no differences in distribution of adverse events were noted between the treatment arms.ConclusionsInhaled CO is well tolerated and can be safely administered to patients with IPF in the ambulatory setting; however, inhaled CO did not result in significant changes in study end points. Our findings support testing the efficacy of inhaled therapies in future IPF clinical trials.Trial registryClinicalTrials.gov; No.: NCT01214187; URL: www.clinicaltrials.gov.