Severe Airflow Obstruction Research Articles

Association of Plasma Heat Shock Protein 70 with Disease Severity, Smoking and Lung Function of Patients with Chronic Obstructive Pulmonary Disease.

Extracellular heat shock protein 70 (eHsp70) might modulate immune responses in chronic obstructive pulmonary disease (COPD). The aim of the study was to explore eHsp70 concentration in stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment. Plasma samples were collected from 137 COPD patients and 95 healthy individuals, and concentration of eHsp70 was assessed by commercially available enzyme-linked immunosorbent assay (ELISA) kit (Enzo Life Science, Farmingdale, NY, USA). COPD patients were subdivided regarding airflow obstruction severity and symptoms severity according to the Global Initiative for COPD (GOLD) guidelines. eHsp70 concentration increased in COPD patients when compared to controls and increased with the severity of airflow limitation as well as symptoms burden and exacerbation history. eHsp70 concentration did not differ among COPD patients based on smoking status, yet it increased in healthy smokers compared to healthy nonsmokers. In addition, eHsp70 negatively correlated with lung function parameters forced expiratory volume in one second (FEV1) and FEV1/ forced vital capacity (FVC), and positively with COPD multicomponent indices BODCAT (BMI, airflow obstruction, dyspnea, CAT score), BODEx (BMI, airflow obstruction, dyspnea, previous exacerbations), CODEx (Charlson’s comorbidity index, airflow obstruction, dyspnea, previous exacerbations) and DOSE (dyspnea, airflow obstruction, smoking status, previous exacerbations) With great predictive value (OR = 7.63) obtained from univariate logistic regression, eHsp70 correctly classified 76% of cases. eHsp70 is associated with COPD prediction and disease severity and might have the potential for becoming an additional biomarker in COPD assessment.

Mechanisms of orthopnoea in patients with advanced COPD

Many patients with severe chronic obstructive pulmonary disease (COPD) report an unpleasant respiratory sensation at rest, which is further amplified by adoption of a supine position (orthopnoea). The mechanisms of this acute symptomatic deterioration are poorly understood.Sixteen patients with advanced COPD and a history of orthopnoea and 16 age- and sex-matched healthy controls underwent pulmonary function tests (PFTs) and detailed sensory-mechanical measurements including inspiratory neural drive (IND) assessed by diaphragm electromyography (EMGdi), oesophageal pressure (P es) and gastric pressure (P ga), in both sitting and supine positions.Patients had severe airflow obstruction (forced expiratory volume in 1 s (FEV1): 40±18% pred) and lung hyperinflation. Regardless of the position, patients had lower inspiratory capacity (IC) and higher IND for a given tidal volume (V T) (i.e. greater neuromechanical dissociation (NMD)), higher intensity of breathing discomfort, higher minute ventilation (V'E) and higher breathing frequency (f B) compared with controls (all p<0.05). For controls in a supine position, IC increased by 0.48 L versus sitting erect, with a small drop in V'E, mainly due to reduced f B (all p<0.05). By contrast, IC remained unaltered in patients with COPD, but dynamic lung compliance (C Ldyn) decreased (p<0.05) in the supine position. Breathing discomfort, inspiratory work of breathing (WOB), inspiratory effort, IND, NMD and neuroventilatory uncoupling all increased in COPD patients in the supine position (p<0.05), but not in the healthy controls. Orthopnoea was associated with acute changes in IND (r=0.65, p=0.01), neuroventilatory uncoupling (r=0.76, p=0.001) and NMD (r=0.73, p=0.002).In COPD, onset of orthopnoea coincided with an abrupt increase in elastic loading of the inspiratory muscles in recumbency, in association with increased IND and greater NMD of the respiratory system.

Association of overlap syndrome with incident atrial fibrillation

Increasingly compelling data link chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) to cardiovascular complications independent of known comorbidities. It remains unclear whether the association is amplified in the presence of both conditions. The aims of this study are to assess the prevalence of atrial fibrillation (AF) in overlap syndrome (OS) and to identify risk factors predisposing to this atrial arrhythmia. We conducted a retrospective cohort study of 268 adults without past or current AF who were referred for an initial diagnostic polysomnogram from 2012 to 2019. A logistic regression analysis was performed to identify risk factors for incident AF. Incident AF occurred in 64 subjects [cumulative probability 24%, 95% confidence interval (CI) 19-29]. Independent predictors of incident AF were age-adjusted Charlson index [Odds ratio (OR) 1.62; 95% confidence interval (CI) 1.3-2.0], percentage of time spent with O2 saturation below 90% (CT90) (OR 3.72, 95% CI 1.18-11.71), and CPAP adherence (OR 0.32, 95% CI 0.13-0.71). OS patients with AF experienced higher hospitalization rates (OR 1.25, 95% CI 1.03-2.37) and worse mortality rates (OR 1.92, 95% CI 1.04-3.54). In multivariate Cox proportional regression, age-adjusted Charlson Index, severity of airflow obstruction, and CPAP adherence were independent predictors of mortality. The burden of hypoxemia and severity of comorbidities are independent factors for incident AF in individuals with OS. CPAP adherence may mitigate the risk of AF and reduce the rate of mortality in this population.

Acute exacerbations of COPD versus IPF in patients with combined pulmonary fibrosis and emphysema

RationalePatients with combined pulmonary fibrosis and emphysema (CPFE) may develop acute exacerbations of IPF (AE-IPF) or COPD (AE-COPD). The incidence and the characteristics of exacerbations in patients with CPFE (e.g., COPD vs IPF) have not been well described.ObjectivesTo compare the incidence and rate of exacerbations in patients with CPFE vs. IPF and evaluate their effect on clinical outcomes.MethodsComprehensive clinical data from CPFE and IPF patients were retrospectively reviewed. Baseline characteristics including lung function data, oxygen requirements, and pulmonary hemodynamics, were collected. Acute exacerbation events in both groups were defined clinically and radiographically. In the CPFE group, two patterns of exacerbations were identified. AE-COPD was defined clinically by symptoms of severe airflow obstruction causing respiratory failure and requiring hospitalization. Radiographic data were also defined based on previously published literature. AE-IPF was defined clinically as an acute hypoxic respiratory failure, requiring hospitalization and treatment with high dose corticosteroids. Radiographically, patients had to have a change in baseline imaging including presence of ground-glass opacities, interlobular septal thickening or new consolidations; that is not fully explained by other etiologies.ResultsEighty-five CPFE patients were retrospectively compared to 112 IPF patients. Of 112 patients with IPF; 45 had AE-IPF preceding lung transplant (40.18%) compared to 12 patients in the CPFE group (14.1%) (p < 0.05). 10 patients in the CPFE group experienced AE-COPD (11.7%). Patients with AE-IPF had higher mortality and more likely required mechanical ventilation and extracorporeal membrane oxygenation (ECMO) compared to patients with AE-COPD, whether their underlying disease was IPF or CPFE.ConclusionsCPFE patients may experience either AE-IPF or AE-COPD. Patients with CPFE and AE-COPD had better outcomes, requiring less intensive therapy compared to patients with AE-IPF regardless if underlying CPFE or IPF was present. These data suggest that the type of acute exacerbation, AE-COPD vs AE-IPF, has important implications for the treatment and prognosis of patients with CPFE.

Diffusing capacity in normal-for-age spirometry and spirometric impairments, using reference equations from the global lung function initiative.

Reference equations from the Global Lung Function Initiative (GLI) are now available for both spirometry and diffusion. However, respiratory phenotypes defined by GLI-based measures of diffusion have not yet been evaluated in GLI-based normal-for-age spirometry or spirometric impairments. We evaluated cross-sectional data from 2100 Caucasians, aged 40-85 years. GLI-based spirometric categories included normal-for-age and the impairments of restrictive-pattern and three-level severity of airflow-obstruction (mild, moderate, severe). GLI-based diffusion included diffusing capacity of the lung for carbon monoxide (DLCO) and measured components of alveolar volume (VA) and transfer coefficient (KCO): DLCO=[VA]x[KCO]. Using multivariable regression models, adjusted odds ratios (adjORs) for DLCO, VA, and KCO<lower limit of normal (LLN) were calculated for spirometric impairments, relative to normal-for-age spirometry. Relative to normal-for-age spirometry, the restrictive-pattern increased the adjORs (95% confidence intervals) for DLCO and VA<LLN-4.61 (3.62, 5.85) and 15.53 (11.8, 20.4), respectively, but not for KCO<LLN-1.02 (0.79, 1.33). Also relative to normal-for-age spirometry, airflow-obstruction from mild to severe increased the adjORs for DLCO<LLN-from 1.22 (0.80, 1.86) to 6.63 (4.91, 8.95), for VA<LLN-from 1.37 (0.85, 2.18) to 7.01 (5.20, 9.43), and for KCO<LLN-from 2.04 (1.33, 3.14) to 3.03 (2.29, 3.99). Notably, in normal-for-age spirometry, 34.5%, 19.7%, and 25.3% of participants had DLCO, VA, or KCO<LLN, respectively. Abnormal diffusion is most prevalent in spirometric impairments but also occurs in normal-for-age spirometry. These results further inform the respiratory phenotypes of GLI-based spirometric categories and, in turn, the spirometric evaluation of respiratory disease.

MiR-223 plays a protecting role in neutrophilic asthmatic mice through the inhibition of NLRP3 inflammasome

BackgroundNeutrophilic subtype asthma occurs in approximately 15–25% of the asthma cases and is associated with severe airflow obstruction, corticosteroid resistance. MicroRNA plays a vital role in regulating many immune processes, but how miRNA circuits coordinate airway inflammation during neutrophilic asthma is unclear.MethodsTo investigate the molecular mechanism of miR-223 in regulation of neutrophilic airway inflammation, miR-223 knockout mice were used to the OVA/CFA-induced neutrophilic asthma or treated with NLRP3 inhibitor and IL-1β receptor antagonist. Based on the results obtained, wide-type mice were subsequently treated with miR-223 agomirs or negative control agomirs, and the effects on airway inflammation were assessed using morphometric techniques, quantitative RT-PCR, western blot, ELISA and other molecular approaches.ResultsThe expression of miR-223 was upregulated in lung tissues of experimental mice model. Furthermore, miR-223−/− mice led to aggravated neutrophilic airway inflammation with heightened histopathological, inflammatory cells and cytokines readouts. Moreover, miR-223−/− mice also presented with enhanced NLRP3 inflammasome level with elevated IL-1β. Blocking NLRP3 or IL-1β diminished this phenotype. Finally, overexpression of miR-223 via treatment with miR-223 agomirs attenuated airway inflammation, NLRP3 levels and IL-1β release.ConclusionsThe findings of this study revealed a crucial role for miR-223 in regulating the immunoinflammatory responses by depressing the NLRP3/ IL-1β axis in neutrophilic asthma.

Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis

BackgroundRevefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD.MethodsA post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV1, St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%–< 50% and < 30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥ 12% and ≥ 200 mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (> 65 and > 75 years), and comorbidity risk factors.ResultsRevefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio > 2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio > 2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged > 75 years.ConclusionsRevefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD.Trial registrationClinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; prospectively registered 22 May 2015] and 0127 [NCT02512510; prospectively registered 28 July 2015]).

Association of dietary quality indices with sleep quality in chronic obstructive pulmonary disease patients

PurposePatients with chronic obstructive pulmonary disease (COPD) suffer from many health problems including poor sleep. This paper aims to evaluate the relationship between diet quality indices (DQIs) and sleep quality in COPD.Design/methodology/approachThe current cross-sectional study was carried on 121 COPD patients. Subjective quality of sleep was determined by Pittsburgh Sleep Quality Index (PSQI) and categorized into “poor” and “good” sleep quality. Dietary history was assessed by the DQIs. Disease status was categorized according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines.FindingsIn total, 103 men and 18 women with a mean age of 66.1 ±10.9 were studied. The subjects were categorized into four groups based on GOLD; 3.3% of subjects were at Stage 1, 38% in Stage 2, 38% in Stage 3 and 20.7% in Stage 4. In total, 38% of subjects were good, and 62% were bad sleepers according to PSQI score. There was no significant relationship between the severity of COPD and PSQI score. We observed a significant inverse relation between PSQI total score and Mediterranean diet (MED) scale, Healthy Eating Index (HEI)-2010 and HEI-2005 (p= 0.024, 0.037 and 0.024, respectively) in males.Originality/valueThis study showed a high prevalence of poor quality of sleep and sleep disturbances among COPD patients. There was an inverse association between PSQI and sleep disorders and DQIs scores in COPD patients. Regardless of the severity of airflow obstruction, poor diet quality may constitute a risk factor for sleep quality.

Re-evaluation of the Uplift Clinical Trial Using Age-Appropriate Spirometric Criteria

The clinical trial of tiotropium in COPD, UPLIFT, enrolled adults with a mean age of 65 years and moderate-to-severe airflow obstruction, based on criteria from the Global Initiative for Chronic Obstructive Lung Disease (GOLD). For the UPLIFT cohort, however, GOLD-based criteria are not age-appropriate. Will the use of more age-appropriate criteria for airflow obstruction from the Global Lung Function Initiative (GLI) modify the spirometric classification of the UPLIFT cohort and, in turn, the mortality effect of tiotropium in COPD? Baseline spirometric classifications were first cross-tabulated by GLI- and GOLD-based criteria. Next, in GLI- and GOLD-based airflow obstruction, modified intention-to-treat analyses evaluated differences in time to death over 4 years, comparing tiotropium vsplacebo. Because treatment response may differ by COPD severity, the mortality effect also was evaluated within stratum defined by GLI- and GOLD-based moderate and severe airflow obstruction. Of 5,898 participants with GOLD-based airflow-obstruction, staged as moderate in 2,739 (46.4%) and severe in 3,156 (53.5%), GLI-based criteria established airflow obstruction in 5,750 (97.5%), staged as moderate in 795 (13.5%) and severe in 4,947 (83.9%). Relative to placebo, tiotropium yielded statistically nonsignificant adjusted hazard ratios (adjHRs) (95%CI) for death of 0.91 (0.80-1.04) and 0.91 (0.79-1.03) in GLI- and GOLD-based airflow obstruction, respectively. However, statistically significant effect modification was observed, but only in GLI-based moderate and severe airflow-obstruction, with tiotropium yielding adjHRs for death of 0.53 (0.34-0.81) and 0.99 (0.86-1.13), respectively. The P value for interaction was .007. Mortality reduction by tiotropium was only statistically significant in GLI-based moderate airflow-obstruction, a group that was underrepresented in UPLIFT because of severity misclassification by the original GOLD-based enrollment criteria.

Bronchial thermoplasty reduces airway resistance

BackgroundThe mechanism for symptomatic improvement after bronchial thermoplasty (BT) is unclear, since spirometry reveals little or no change. In this study, the effects of BT on airway resistance were examined using two independent techniques.MethodsEighteen consecutive patients, with severe asthma (57.6 ± 14.2 years) were evaluated by spirometry and plethysmography at three time points: (i) baseline, (ii) left lung treated but right lung untreated and (iii) 6 weeks after both lungs were treated with BT. At each assessment, total and specific airway resistance (Raw, sRaw) were measured. High resolution CT scans were undertaken at the first two assessments, and measurements of lobar volume, airway volume and airway resistance were made. The Asthma Control Questionnaire (ACQ) was administered at each assessment.ResultsThe baseline ACQ score was 3.5 ± 0.9, and improved progressively to 1.8 ± 1.2 (p < 0.01). At baseline, severe airflow obstruction was observed, FEV1 44.8 ± 13.7% predicted, together with gas trapping, and elevated Raw at 342 ± 173%predicted. Following BT, significant improvements in Raw and sRaw were observed, as well as a reduction in Residual Volume, increase in Vital Capacity and no change in FEV1. The change in Raw correlated with the change in ACQ (r = 0.56, p < 0.05).CT scans demonstrated reduced airway volume at baseline, which correlated with the increased Raw determined by plethysmography (p = − 0.536, p = < 0.05). Following BT, the airway volume increased in the treated lung, and this was accompanied by a significant reduction in CT-determined local airway resistance.ConclusionSymptomatic improvement after BT is mediated by increased airway volume and reduced airway resistance.

Paradoxical Vocal Fold Motion in Difficult Asthma Is Associated with Dysfunctional Breathing and Preserved Lung Function

Many patients with difficult asthma also have coexisting vocal cord dysfunction (VCD), evident by paradoxical vocal fold motion (PVFM) on laryngoscopy. Among patients with difficult asthma, we sought to identify clinical features associated with laryngoscopy-diagnosed PVFM. Consecutive patients with "difficult asthma" referred by respiratory specialists underwent systematic assessment in this observational study. Those with a high clinical suspicion for VCD were referred for laryngoscopy, either at rest or after mannitol provocation. Statistical analyses were performed to identify clinical factors associated with PVFM, and a multivariate logistic regression model was fitted to control for confounders. Of 169 patients with difficult asthma, 63 (37.3%) had a high clinical probability of VCD. Of 42 who underwent laryngoscopy, 32 had PVFM confirmed. Patients with PVFM more likely had preserved lung function (prebronchodilator forced expiratory ratio 74% ± 11 vs 62% ± 16, P < .001); physiotherapist-confirmed dysfunctional breathing (odds ratio [OR]= 5.52, 95% confidence interval [CI]: 2.4-12.7, P < .001), gastro-oesophageal reflux (OR= 2.6, 95% CI: 1.16-5.8, P=.02), and a lower peripheral eosinophil count (0.09 vs 0.23, P= .004). On multivariate logistic regression, independent predictors for PVFM were dysfunctional breathing (OR= 4.93, 95% CI: 2-12, P < .001) and preserved lung function (OR=1.07, 95% CI: 1.028-1.106, P < .001). Among specialist-referred patients with difficult asthma, VCD pathogenesis may overlap with dysfunctional breathing but is not associated with severe airflow obstruction. Dysfunctional breathing and preserved lung function may serve as clinical clues for the presence of VCD.

Change in [formula omitted]O2peak in Response to Aerobic Exercise Training and the Relationship With Exercise Prescription in People With COPD: A Systematic Review and Meta-analysis

Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O2peak) with aerobic training. The goal of this study was to investigate the effect of aerobic training and exercise prescription on V˙O2peak in COPD. A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring V˙O2peak prior to and following supervised lower-limb aerobic training in COPD. A random effects meta-analysis limited to randomized controlled trials comparing aerobic training vsusual care was conducted. Other study designs were included in a secondary meta-analysis and meta-regression to investigate the influence of program and patient factors on outcome. A total of 112 studies were included (participants, N= 3,484): 21 controlled trials (n= 489), of which 13 were randomized (n= 288) and 91 were uncontrolled (n= 2,995) studies. Meta-analysis found a moderate positive change in V˙O2peak (standardized mean difference, 0.52; 95%CI, 0.34-0.69) with the intervention. The change in V˙O2peak was positively associated with target duration of exercise session (P= .01) and, when studies > 1 year duration were excluded, greater total volume of exercise training (P= .01). Similarly, the change in V˙O2peak was greater for programs > 12weeks compared with those 6 to 12weeks when adjusted for age and sex. However, reported prescribed exercise intensity (P= .77), training modality (P > .35), and mode (P= .29) did not affect V˙O2peak. Cohorts with more severe airflow obstruction exhibited smaller improvements in V˙O2peak (P< .001). Overall, people with COPD achieved moderate improvements in V˙O2peak through supervised aerobic training. There is sufficient evidence to show that programs with greater total exercise volume, including duration of exercise session and program duration, are more effective. Reduced effects in severe disease suggest alternative aerobic training methods may be needed in this population. PROSPERO; No.: CRD42018099300; URL: https://www.crd.york.ac.uk/prospero/.

Relationship between the COPD assessment test (CAT) and respiratory function characteristics of North African stable COPD patients

Introduction: The COPD Assessment Test (CAT) is a simple method for assessing the impact of COPD on the patient`s health which is not validated with North African COPD patients. Objective: To determine the relationship between the CAT score and the SGRQ, anthropometric, dyspnea, severity of airflow obstruction and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages in stable COPD patients. Material and Methods: It is a cross-sectional observational study. It consists of a convenience sample of COPD and Smokers subjects aged more than 30 years. Dyspnea was evaluated according to the modified British medical research council (mMRC) 4). Arabic versions of the SGRQ and CAT questionnaires were used. Spirometry was performed in accordance with international standards. Obstructive ventilator defect (OVD) grades and GOLD grades were identified. Results: A total sample of 150 (121 COPD) was collected. A negative correlation was found between CAT score and anthropometric and all functional parameters in the total sample. Correlations between CAT score and mMRC score, pulmonary age and SGRQ score were found in COPD group (p&lt;0.01). CAT score correlated with OVD and GOLD grades, severe COPD (GOLD 3 and 4) had higher CAT scores. Conclusion: There is a strong relationship between CAT score and clinical and functional COPD components. Impact of this research on clinical medicine and basic science: COPD is a complex disease with multiple consequences which can impede the quality of life of patients. The latter can be evaluated by specific questionnaires. The most used questionnaire is St. George’s Respiratory Questionnaire (SGRQ). However, this health status measure is long and not practical for clinical routine use. Therefore, recently a new simple system evaluating health status was developed. It is the COPD Assessment Test (CAT), which was approved, in its French, English and Arabic version. It is a simple method for assessing the impact of COPD on the patient`s health. CAT is composed of only eight questions and a key is not needed to calculate a score. To our own knowledge, there are no studies about CAT scoring in and its relation with clinical and respiratory function characteristics in North Africa. Keywords: COPD- CAT score- SGRQ-FEV1- Spirometry

Presence or Absence of Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease is Associated With Distinct Phenotypes

IntroductionReduced skeletal muscle function and cognitive performance are common extrapulmonary features in Chronic Obstructive Pulmonary Disease (COPD) but their connection remains unclear. Whether presence or absence of skeletal muscle dysfunction in COPD patients is linked to a specific phenotype consisting of reduced cognitive performance, comorbidities and nutritional and metabolic disturbances needs further investigation. MethodsThirty-seven patients with COPD (grade II–IV) were divided into two phenotypic cohorts based on the presence (COPD dysfunctional, n=25) or absence (COPD functional, n=12) of muscle dysfunction. These cohorts were compared to 28 healthy, age matched controls. Muscle strength (dynamometry), cognitive performance (Trail Making Test and STROOP Test), body composition (Dual-energy X-Ray Absorptiometry), habitual physical activity, comorbidities and mood status (questionnaires) were measured. Pulse administration of stable amino acid tracers was performed to measure whole body production rates. ResultsPresence of muscle dysfunction in COPD was independent of muscle mass or severity of airflow obstruction but associated with impaired STROOP Test performance (p=0.04), reduced resting O2 saturation (p=0.003) and physical inactivity (p=0.01), and specific amino acid metabolic disturbances (enhanced leucine (p=0.02) and arginine (p=0.06) production). In contrast, COPD patients with normal muscle function presented with anxiety, increased fat mass, plasma glucose concentration, and metabolic syndrome related comorbidities (hypertension and dyslipidemia). ConclusionCOPD patients with muscle dysfunction show characteristics of a cognitive – metabolic impairment phenotype, influenced by the presence of hypoxia, whereas those with normal muscle function present a phenotype of metabolic syndrome and mood disturbances.

Clinical profile of patients with chronic obstructive pulmonary disease at a tertiary care hospital

Background: Chronic obstructive pulmonary disease progresses if the exposure to aggravating factors continues. As lung function is declined, even after exposure is reduced or totally stopped, the COPD continues to progress though may be at a slower pace and as an effect of increasing age. Objective of the study was to study the clinical profile of patients with chronic obstructive pulmonary disease at a tertiary care hospital.Methods: A hospital based cross sectional study was carried out among 30 patients as decided by inclusion and exclusion criteria at MediCiti Institute of Medical Sciences, Medchal from November 2012 to June 2014. Detailed history, detailed clinical examination, Systemic examination and Forced expiratory volume (FEV1) was done for all patients included. Pack years of smoking was calculated. Data was entered in Excel worksheet and analyzed using proportions.Results: Maximum number of patients was in age group of 60-69 years (36.67%). Majority were males i.e. 83.34%. Smoking was major risk factor. Maximum number of patients (90%) had symptoms of less than one year of duration. Maximum number of patients (80%) had moderate to severe airflow obstruction at time of presentation and only 13.34% had mild disease. Four patients had mild form of the disease. Majority of patients with severe to very severe disease had more than 20 pack years. All patients in the study had breathlessness at the time of presentation. Wheeze and Crepitations were present in 96.66% of patients.Conclusions: Smoking has been found to be the major risk factor and it was positively correlated with the severity of COPD.

Exercise capacity and ventilation inhomogeneity in cystic fibrosis: A cross‐sectional study

Lung clearance index (LCI2.5 ) is a marker of overall lung ventilation inhomogeneity and has proven to be able to detect early peripheral damage in subjects with cystic fibrosis (CF), with greater sensitivity than conventional spirometry. Combining its sensitivity with the output of an incremental exercise testing, we hypothesized that any sign of ventilation inhomogeneity in subjects without severe airflow obstruction and with a normal exercise tolerance could be relevant for the CF team, tracking early lung disease and potential exercise limiting factors. Patients with CF in clinical stable conditions were recruited between 2015 and 2017. Available spirometry, nitrogen multiple-breath washout test and symptoms-limited exercise testing performed as parts of patients' annual routine evaluation were considered for this cross-sectional study. To describe the relationship between exercise intensity and ventilation inhomogeneity, a linear regression analysis was performed using backward elimination based on Akaike information criteria. Seventy-seven patients (38 females) were included. Sacin and LCI2.5 were significantly higher in patients with an overall reduced exercise tolerance. Peak work developed during exercise was associated with body mass index (b = 5.25; 95% confidence interval [CI] = 1.53-8.98), forced expiratory volume in 1 second (FEV1 ; b = 3.71; 95% CI = 1.96-5.46), Pseudomonas aeruginosa chronic infection (b = -8.84; 95% CI = -15.84 to -1.84) but not with LCI2.5 . Exercise capacity and airflow obstruction are associated in this Italian CF cohort. Considering the greater discriminatory power of LCI2.5 over FEV1 and peak work, the Godfrey protocol without gas analysis cannot provide detailed information about lung function or efficiency. However, this incremental protocol without gas exchange measures can still provide the CF team with information about exercise tolerance and disability.

Effects of Lung Function-Related Genes and TSLP on COPD Phenotypes

A weighted genetic risk score (GRS) based on 16 SNPs implicated in reduced lung function in both Japanese and non-Japanese populations was previously associated with the onset of COPD and asthma. We here examine the genetic impact of this lung function GRS on specific COPD phenotypes. A cohort of Japanese COPD patients (N = 270) underwent lung function testing followed by genotyping with allele-specific arrays for 16 SNPs as well as expression quantitative trait loci at TSLP (rs2289276, rs3806933). Lung function GRS scoring and two-step cluster analyses grouped patients into different COPD phenotypes based on gender, age, smoking index, %FEV1 and lung function GRS. The genetic effect of TSLP on COPD phenotypes was also examined for interactions with the lung function GRS. A total of 270 participants were grouped into 5 clusters. The cluster with the highest levels of lung function GRS was characterized by moderate to severe airflow obstruction and the highest blood eosinophil counts. Regarding TSLP, an increased number of T alleles at both SNPs was found in the cluster characterized by moderate to severe airflow obstruction and heavy smoking (rs2289276, p value = 0.035; rs3806933, p value = 0.047) independent of the lung function GRS. A genetic susceptibility to impaired lung function carries an increased risk of developing COPD characterized by increased eosinophil counts and severe airflow obstruction while individuals with increased TSLP responses to external stimuli have an independent risk of developing severe airflow obstruction in the presence of heavy smoking.

Point of Care Portable Spirometry in the Diagnosis and Treatment of Inpatients with Chronic Obstructive Pulmonary Disease.

Spirometry is required to accurately diagnose chronic obstructive pulmonary disease (COPD). Following an acute exacerbation, it is recommended that spirometry be performed after a delay of 4-6weeks to allow stability and a measure of 'baseline' lung function. However, poor attendance at these appointments can occur, leading to an inability to confirm the diagnosis of COPD or assess the severity of airflow obstruction. Portable spirometry (PS) is a proven surrogate device that may provide a convenient method to address these issues. The purpose of this study was to compare PS values, obtained prior to hospital discharge to laboratory-based spirometry (LS) results undertaken 4weeks later. Thirty-three eligible inpatients with a clinically determined exacerbation of COPD were recruited. Patients underwent PS prior to discharge and LS 4weeks later. Reliability of PS values at discharge compared with outpatient LS 4weeks later was excellent (intraclass correlation coefficient > 0.9). The PS confirmed a new diagnosis of COPD at the bedside in 29% of patients and excluded COPD in 6% at both time points. Patients were found to have a similar severity of airflow obstruction on both PS and LS, with clinical stability maintained between visits. The PS and LS may be used interchangeably for earlier diagnosis of COPD. PS at the point of discharge from hospital offers a unique opportunity to diagnose and facilitate COPD management from hospital to primary care.

Influence of pulmonary rehabilitation in patients with Chronic Obstructive Pulmonary Disease exacerbator phenotype.

Objective To verify if there are differences in Chronic Obstructive Pulmonary Disease (COPD) patient exacerbator and non-exacerbator phenotypes undergoing a Pulmonary Rehabilitation Program (PRP). Methods A real life retrospective study included outpatients with COPD from public primary care who completed a 12-weeks PRP, three times a week. All were assessed before and after PRP using the six-minute walk test (6MWT), the modified Medical Research Council (mMRC) dyspnea index, quality of life and Body-mass Index, airflow Obstruction, Dyspnea and Exercise (BODE index). Results A total of 151 patients were analyzed and mean age was 65.0 ± 8.1 years and mean Forced Expiratory Volume (FEV) 1% of predicted was 39.8 ± 15.9. The predominant gender was male (66.9%). Of these patients 31 (20.5%) were exacerbator phenotype There was a significant improvement in the mean distance in the 6MWT in both groups, with the largest change observed in the exacerbator group [mΔ (95% CI): 84.9 (57.1-112.6) vs. 48.6 (37-60.2) p= 0.018]. Significant reduction in dyspnea on the mMRC scale occurred in both groups, with the highest intensity in the exacerbator group [mΔ (95% CI): - 0.8 (-1.11 to 0.51) vs. -1.6 (-2.20 to -1.13) p = 0.006]. Improvement in the BODE index occurred in both groups, but the mean variation was also significantly greater in the exacerbator group [mΔ (95% CI): -1.44 (-2.17 to -0.70) p= 0.045]. Conclusion Patients with COPD exacerbator phenotype had a greater magnitude of response to PRP (36 meters) when compared to non-exacerbator phenotype regardless the severity of airflow obstruction, also showing improvement in prognosis measured by the BODE index.

Efficacy and safety of revefenacin for nebulization in patients with chronic obstructive pulmonary disease taking concomitant ICS/LABA or LABA: subgroup analysis from phase III trials.

Background:Combinations of a long-acting muscarinic receptor antagonist (LAMA), long-acting β-agonist (LABA), and inhaled corticosteroid (ICS) are used for patients with persistent chronic obstructive pulmonary disease (COPD) exacerbations on bronchodilator monotherapy. In this prespecified subgroup analysis, we assessed the efficacy and safety of the LAMA revefenacin in patients with COPD taking concomitant LABA, including ICS/LABA (LABA subgroup).Methods:Efficacy data were obtained from two 12-week, replicate, placebo-controlled trials and safety data were pooled from the 12-week and a 52-week tiotropium-controlled trial. Patients received revefenacin 175 µg or placebo in the 12-week or tiotropium 18 µg in the 52-week studies. The efficacy endpoint was least squares (LS) mean change from baseline in trough forced expiratory volume in 1 second (FEV1). Clinical health outcomes were assessed using the St. George’s Respiratory Questionnaire (SGRQ).Results:Revefenacin produced similar improvements from baseline in trough FEV1 in the non-LABA and LABA subgroups [placebo-adjusted LS mean change (95% confidence interval) in day 85 trough FEV1, 150.9 (110.3−191.6) ml and 139.2 (82.9−195.5) ml; p < 0.0001 versus placebo]. Similar improvements were observed in SGRQ scores in the non-LABA and LABA subgroups [−3.3 (−5.4 to −1.2) and −3.4 (−6.3 to −0.6)]. Improvements in lung function and health outcomes were observed regardless of airflow obstruction severity. Revefenacin was well tolerated with more adverse events reported in the LABA than the non-LABA subgroup.Conclusions:Once daily revefenacin for nebulization can be an effective and well-tolerated treatment for patients who require concomitant use of LABA with or without ICS.ClinicalTrials.gov identifiers:NCT02512510, NCT02459080, NCT02518139 The reviews of this paper are available via the supplemental material section.