Chronic Obstructive Airways Research Articles

Association of Respiratory Morbidities with Particulate Air Pollution in Delhi, India- A Prospective Study

Abstract Background: Elevated levels of air pollution and long-term exposure can lead to detrimental health conditions, mainly affecting cardiorespiratory systems. Materials and Methods: A prospective observational study was conducted in five sampled hospitals in Delhi. A pre-designed, pre-tested, semi-structured questionnaire was filled out for each patient with data from hospital records. The admission rates were recorded daily over the study period along with the air quality with reference to particulate matter (PM). The trends of the hospital admissions for respiratory morbidity were corroborated with PM 2.5. Descriptive statistics and correlation amongst emergency admissions and air pollutants were analysed using Microsoft Excel. The impact of air quality on the rate of hospitalisation due to respiratory conditions was projected by mathematical modelling. Results: The rate of hospitalisation due to bronchial asthma, chronic obstructive pulmonary disease, bronchitis and lower respiratory tract infections was found to be directly proportional to an increase in PM2.5. Conclusion: The healthcare system is increasingly strained and thus, the additional burden due to rising air pollution needs to be prevented by making people aware about the methods of reducing air pollution.

Immunomodulatory activity of omadacycline in vitro and in a murine model of acute lung injury.

Cystic fibrosis (CF) is characterized by chronic airway obstruction, infection, and inflammation leading to progressive loss of lung function and eventual respiratory failure. Omadacycline, a tetracycline antibiotic, demonstrates in vitro activity against key CF pathogens, substantial lung penetration, and increasing clinical evidence for the treatment of lung infections in people with CF (PwCF). Preliminary in vitro data demonstrate that omadacycline exhibits anti-inflammatory activity. This study aims to determine the anti-inflammatory effects of omadacycline in vitro and in a murine model of lipopolysaccharide (LPS)-induced lung neutrophilia. In vitro, THP-1-derived macrophages were treated with omadacycline (20-100 µg/mL) 30 minutes prior to LPS stimulation. Pro-inflammatory cytokine (TNF-α, IL-1β/6), chemokine (CXCL-1/2), and MMP-9 levels were analyzed after 24 hours by ELISA. Omadacycline's effects on IL-8-induced human neutrophil chemotaxis were also investigated. In vivo, omadacycline (2.5-30 mg/kg), comparators dexamethasone (1 mg/kg), and azithromycin (30 mg/kg) were administered 1 hour before and 6 hours after intranasal LPS challenge, respectively. Leukocyte counts and differentials in bronchoalveolar lavage fluid (BALF), inflammatory mediator levels in BALF and lung homogenates, pulmonary edema markers, and the severity of lung injury were evaluated 24 hours or 48 hours post-challenge. Treatment with omadacycline in vitro resulted in significant, dose-dependent reductions in IL-6, CXCL-1, and MMP-9 expression and inhibition of IL-8-induced neutrophil chemotaxis. In vivo, omadacycline yielded protective and therapeutic effects by reducing the production of proinflammatory cytokines and chemokines and neutrophil infiltration into the lungs, along with modestly improving lung injury severity. These preclinical results suggest that omadacycline may provide dual anti-bacterial and anti-inflammatory activities relevant to chronic lung infection treatment in PwCF.IMPORTANCENontuberculous mycobacteria, particularly Mycobacterium abscessus complex (MABSC), are a major concern for people with cystic fibrosis (PwCF) due to their association with deteriorating lung function. A substantial barrier to effective treatment is the limited number of safe and effective antibiotics. Omadacycline offers a potential advancement in managing MABSC infections in cystic fibrosis due to its activity, effective penetration into pulmonary secretions, improved tolerability, and good oral bioavailability as shown in healthy volunteers. Our study is the first to explore omadacycline's effects in a model of sterile lung inflammation and acute lung injury. We found that omadacycline not only has potent anti-bacterial properties but also exhibits anti-inflammatory effects, reducing lung inflammation and injury in our preclinical models. These findings underscore omadacycline's potential as a dual-action therapy for lung infections in PwCF, indicating significant potential to improve patient outcomes and guide more effective antimicrobial therapy decisions.

A Study on the Correlation Between Sarcopenia and Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a disease that affects the entire body. Sarcopenia, one of the adverse manifestations of the whole body, can lead to a variety of adverse outcomes. The worldwide studies have shown that sarcopenia was associated with COPD. This article aims to further enrich this research direction by focusing on the relationship between sarcopenia and COPD in Chinese inpatients. The subjects of this study were patients hospitalized in the Department of Respiratory and Critical Care Medicine of Rongchang People's Hospital of Chongqing from July 2022 to May 2024. After bioelectrical impedance analysis (BIA), test of 6 m walking speed, and tests for upper grip strength were accomplished, the sarcopenia can be diagnosed. According to the presence of chronic airflow limitation, which assessed by post-bronchodilator spirometry, we diagnosed COPD. COPD and sarcopenia as two variables, simple correlation analysis was adopted for them. The subjects were classified into sarcopenia group and non-sarcopenia group. And then, the correlation between sarcopenia and COPD was assessed with binary logistic regression analysis. Finally we get the results. Spearman's correlation coefficient for sarcopenia and COPD was 0.166 (p<0.05). While, COPD was not an independent risk factor to sarcopenia in the binary logistic regression analysis. Therefore, this study draws conclusions that COPD and sarcopenia is associated, but not linked independently.

Psychiatric Disorders in Patients with Chronic Obstructive Pulmonary Disease: Clinical Significance and Treatment Strategies.

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease characterized by chronic airflow limitation and persistent respiratory symptoms. It is a major cause of morbidity and mortality worldwide, significantly impacting healthcare systems with considerable socioeconomic consequences. The main risk factors include exposure to tobacco smoke, environmental pollutants, occupational dust, and genetic factors such as alpha-1 antitrypsin deficiency. COPD is often associated with extrapulmonary comorbidities, particularly psychiatric disorders like depression and anxiety, which worsen patients' quality of life and prognosis. The prevalence of these disorders in patients with COPD varies significantly but is always higher than in healthy controls. Psychiatric disorders can negatively influence COPD management and vice versa, creating a complex bidirectional interaction. Depression and anxiety are the most common psychiatric comorbidities in patients with COPD, influenced by factors such as social isolation, physical limitations, and fear of exacerbations. Diagnosis of these psychiatric disorders is complicated by the overlap of symptoms with those of COPD. However, some screening tools can facilitate early detection. The treatment of psychiatric disorders in patients with COPD in a rehabilitation setting requires a multidisciplinary approach involving pulmonologists, neurologists and psychologists. Pharmacological therapy with antidepressants shows mixed results in terms of efficacy and safety, with some studies reporting benefits on quality of life and others suggesting an increased risk of exacerbations and pneumonia. An integrated approach that includes the assessment and intervention of mental disorders is essential to improve the overall management of COPD and the quality of life of patients. This narrative review provides an overview of the main psychiatric comorbidities in COPD patients, aiming to fill gaps in the literature and suggest areas for future research.

Abnormal spirometric patterns and respiratory symptoms in HIV patients with no recent pulmonary infection in a periurban hospital in Ghana.

Human immunodeficiency virus (HIV) infection is associated with chronic airway obstruction, even in patients who have achieved viral suppression from combination antiretroviral treatment (cART). Spirometry is a supplementary test that aids in diagnosing pulmonary dysfunction in people living with HIV. To compare the prevalence of spirometric abnormalities among cART-treated HIV patients and cART-naïve HIV patients with non-HIV controls with no recent history of pulmonary infection in a peri-urban hospital in Ghana. In a case-control design, spirometry was performed in 158 cART-treated HIV patients, 150 cART-naïve HIV patients and 156 non-HIV controls. Clinical, sociodemographic data and respiratory symptoms were collected using a structured questionnaire. Spirometric abnormalities were categorised as obstructive (OSP) or restrictive (RSP) spirometric patterns based on the Cameroonian reference equation. The prevalence of OSP was higher in the cART-treated and cART-naïve HIV patients compared to non-HIV controls (13.9% vs 10.7% vs 5.1% respectively, p = 0.026), whereas that of RSP was similar among the study groups. Respiratory symptoms were common among cART-treated and cART-naïve HIV patients compared to non-HIV controls (48.1% vs 40% vs 19.2% respectively, p < 0.001). The major factors associated with OSP were female gender [OR (95% CI) = 2.46 (1.09-5.13), p = 0.031], former cigarette smoking [1.92 (1.04-3.89), p < 0.001], exposure to medium-to-high levels of biomass [3.07 (1.16-8.73), p = 0.019], presence of a respiratory symptom [1.89 (1.11-5.08), p = 0.029] and unemployment [3.26 (1.19-8.95), p = 0.042]. The major determinants of RSP were age, female gender [1.74 (1.05-4.29), p = 0.041], former cigarette smoking [2.31 (1.27-6.77), p < 0.001] and medium-to-high biomass exposure [1.58 (1.06-5.37), p = 0.043]. In HIV patients without any recent pulmonary infection in a peri-urban area of Ghana, there was a higher prevalence of OSP among cART-treated and cART naïve HIV patients compared to the non-HIV control. However, the prevalence of RSP was similar among HIV patients and non-HIV controls.

Validation of diagnostic coding for chronic obstructive pulmonary disease in an electronic health record system in Hong Kong.

Electronic health record databases can facilitate epidemiology research regarding diseases such as chronic obstructive pulmonary disease (COPD), a common medical condition worldwide. We aimed to assess the validity of International Classification of Diseases, 9th Revision (ICD-9) code algorithms for identifying COPD in Hong Kong's territory-wide electronic health record system, the Clinical Data Analysis and Reporting System (CDARS). Adult patients diagnosed with COPD at all public hospitals in Hong Kong and specifically at Queen Mary Hospital from 2011 to 2020 were identified using the ICD-9 code 496 (Chronic airway obstruction, not elsewhere classified) within the CDARS. Two respiratory specialists reviewed clinical records and spirometry results to confirm the presence of COPD in a randomly selected group of cases. During the study period, 93 971 and 2479 patients had the diagnostic code for COPD at all public hospitals in Hong Kong and specifically at Queen Mary Hospital, respectively. Two hundred cases were randomly selected from Queen Mary Hospital for validation using medical records and spirometry results. The overall positive predictive value was 81.5% (95% confidence interval=76.1%-86.9%). We also developed an algorithm to identify COPD cases in our cohort. This study represents the first validation of ICD-9 coding for COPD in the CDARS. Our findings demonstrated that the ICD-9 code 496 is a reliable indicator for identifying COPD cases, supporting the use of the CDARS database for further clinical research concerning COPD.

Chronic Airway Obstruction in the Post-COVID-19 Era: Is There a Cause or Effect?

ABSTRACT Introduction: Chronic airway obstruction (CAO) is the terminology used to address chronic obstructive airway diseases, namely bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), bronchiectasis, and posttuberculosis (TB) COPD. We studied the profile of the CAO at the respiratory medicine department post the COVID-19 lockdown to understand any cause or effect of past COVID-19. Materials and Methods: This prospective observational study enrolled 164 cases of CAO. Clinical and radiological details of the two groups of CAO with and without a past history of COVID-19 were noted. Results: Of 164, 101 (61.59%) were men and 63 (38.41%) were women. Thirty-nine had a history of COVID-19. Of the 164 cases, 39 (23.7%) had BA, 51 (31.09%) had COPD, 61 (37.19%) had post-TB COPD, and 13 (7.92%) had bronchiectasis. In patients with a history of COVID-19, 9 (23.1%) had BA, 9 (23.1%) had COPD, 15 (38.5%) had post-TB COPD, and 6 (15.3%) had bronchiectasis. Eight had normal lung functions, 4 had mild obstructions, 75 had moderate obstruction, and 74 had severe obstructions. The clinical and spirometry differences in those with and without a history of COVID-19 were statistically insignificant. On high-resolution computed tomography thorax, 46 (28.1%) had emphysema, 16 (9.7%) had air trapping, 65 (39.7%) had fibrobronchiectasis, and 37 (22.5%) were normal. In patients with a history of COVID-19, 6 (15.3%) had emphysema, 2 (5.2%) had air trapping, 23 (58.9%) had fibrobronchiectasis, and 8 (20.5%) were normal. The difference in radiological findings was statistically significant and more in the group with a history of COVID-19 (P = 0.029). Conclusion: COVID-19 did not affect the distribution, clinical characteristics of CAO, however, impacted radiological findings significantly.

Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.

Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure. To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population. We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7. The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCO<LLN) 5.7% and for emphysema 8.8%, with a higher prevalence in current smokers than in ex-smokers and never-smokers. The proportion of never-smokers among those with CAL, emphysema and impaired DLCO was 32%, 19% and 31% respectively. Regardless of smoking habits, the prevalence of respiratory symptoms was higher among people with CAL and impaired DLCO, compared to those with normal lung function. Asthma prevalence in never-smokers with CAL was 14%. In this group, asthma associated with lower FEV1 and more respiratory symptoms. In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

A comprehensive analysis of the health effects associated with smoking in the largest population using UK Biobank genotypic and phenotypic data

BackgroundSmoking is a widespread behavior, while the relationship between smoking and various diseases remains a topic of debate. ObjectiveWe conducted analysis to further examine the identified associations and assess potential causal relationships. MethodsWe utilized seven single nucleotide polymorphisms (SNPs) known to be linked to smoking extracting genotype data from the UK Biobank, a large-scale biomedical repository encompassing comprehensive health-related and genetic information of European descent. Phenome-wide association study (PheWAS) analysis was conducted to map the association of genetically predicted smoking status with 1,549 phenotypes. The associations identified in the PheWAS were then meticulously examined through two-sample Mendelian randomization (MR) analysis, utilizing data from the UK Biobank (n = 487,365) and the Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) (n = 337,334). This approach allowed us to comprehensively characterize the links between smoking and disease patterns. ResultsThe PheWAS analysis produced 34 phenotypes that demonstrated significant associations with smoking (P = 0.05/1460). Importantly, sickle cell anemia and type 2 diabetes exhibited the most significant SNPs (both 85.71% significant SNPs). Furthermore, the MR analyses provided compelling evidence supporting causal associations between smoking and the risk of following diseases: obstructive chronic bronchitis (IVW: Beta = 0.48, 95% confidence interval (CI) 0.36-0.61, P = 1.62×10−13), cancer of the bronchus (IVW: Beta = 0.92, 95% CI 0.68-1.17, P = 2.02×10−13), peripheral vascular disease (IVW: Beta = 1.09, 95% CI 0.71-1.46, P = 1.63×10−8), emphysema (IVW: Beta = 1.63, 95% CI 0.90-2.36, P = 1.29×10−5), pneumococcal pneumonia (IVW: Beta = 0.30, 95% CI 0.11-0.49, P = 1.60×10−3), chronic airway obstruction (IVW: Beta = 0.83, 95% CI 0.30-1.36, P = 2.00×10−3) and type 2 diabetes (IVW: Beta = 0.53, 95% CI 0.16-0.90, P = 5.08×10−3). ConclusionThis study affirms causal relationships between smoking and obstructive chronic bronchitis, cancer of the bronchus, peripheral vascular disease, emphysema, pneumococcal pneumonia, chronic airway obstruction, type 2 diabetes, in the European population. These findings highlight the broad health impacts of smoking and support smoking cessation efforts.

Tobacco smoking-attributable mortality in Kenya, 2012-2021.

Tobacco smoking poses a significant risk for various diseases, including cardiovascular diseases, chronic respiratory diseases, and cancers. In Kenya, tobacco-related deaths contribute substantially to non-communicable disease mortality. This study aims to quantify the mortality attributed to tobacco smoking in Kenya from 2012 to 2021. Employing a prevalence-based analysis model, the study utilized population attributable fraction (PAF) to estimate age-specific smoke attributable mortality (SAM) rates for individuals aged ≥35 years. Causes of death associated with tobacco use, including cancers, cardiovascular diseases, respiratory diseases, tuberculosis, and diabetes, were analyzed based on age, sex, and death records between 2012 and 2021. Over the study period, 60228 deaths were attributed to tobacco-related diseases, with an annual increase observed until 2016 and subsequent fluctuations. Respiratory diseases, diabetes mellitus, malignant cancers, tuberculosis, and cardiovascular diseases collectively accounted for 16.5% of deaths among individuals aged ≥35 years. Notable contributors were pneumonia and influenza (respiratory diseases), esophageal cancer (cancers), and cerebrovascular diseases (cardiovascular diseases). Of the observed deaths, 16.5% were attributed to smoking, with respiratory diseases (40.5%), malignant cancers (31.4%), tuberculosis (13%), cardiovascular diseases (8.9%), and diabetes mellitus (6.1%) contributing. Pneumonia and influenza, esophageal cancer, chronic airway obstruction, and tuberculosis were primary causes, comprising 70% of all SAM. Tobacco-related mortality is a significant public health concern in Kenya. Efforts should focus on preventing tobacco use and managing associated disease burdens. Smoking cessation initiatives and comprehensive tobacco control measures are imperative to mitigate the impact on population health.

Mitochondria-DNA copy-number in osteoporosis and osteoarthritis among middle-aged women - A population-based cohort study

BackgroundMitochondrial DNA copy number (mtDNA-CN) is associated with aging. A relationship between mtDNA-CN and degenerative disorders, e.g. osteoarthritis (OA) and osteoporosis (OP), has been suggested. We aimed to investigate the relationship of mtDNA-CN and incident OA and OP. Materials and methodsMtDNA-CN was studied in relationship to incident OA and OP in a population-based cohort study of 6916 middle-aged women (52–63 years). Totally 2521 women with sufficient quality of mtDNA were analyzed. After exclusions, 1978 women remained in the study population. Four different endpoints obtained from the National Patient register were studied: 1) OA, 2) OP 3) OA surgery, and 4) OP fracture. In the multivariate model adjustments were made for potential OA and OP risk factors. ResultsWomen with low mtDNA-CN were older and had more activity at work. 125 women (6.32%) were affected by incident OP and 254 women (12.84%) had an OP fracture. Incident OA affected 451 women (22.80%) and 175 women (8.85%) had OA surgery. There were no associations between mtDNA-CN and incident risk of OA (Hazard ratio ​= ​1.00, 95% confidence interval 0.83–1.20), OA surgery (0.79, 0.58–1.07), OP (0.89, 0.62–1.27), or OP fracture (1.00, 0.78–1.29). However, incident OP was significantly associated with T-score (bone density), smoking, diabetes mellitus, and chronic obstructive bronchitis (COPD). OA was associated with body mass index and COPD. ConclusionsThe present study suggests that mtDNA-CN, reflecting mitochondrial dysfunction, is not a major predictor for incident OA or OP. However, due to the limited study size minor associations cannot be excluded.

Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable lung disease. It is characterized by chronic respiratory symptoms and airflow limitation due to abnormalities of the airways caused by continuous exposure to noxious particles or gases. COPD occupies the third position for the cause of death worldwide. The major risk factor for the development of COPD is tobacco smoking. The inhalation of toxic particles, biomass exposure and outdoor air pollution along with other host factors including abnormal lung development and accelerated lung aging can also contribute. Spirometry characterized by non-fully reversible airflow limitation i.e., FEV1/FVC &lt; 0.7 post bronchodilation, confirms the diagnosis of COPD. The major goals of management are to reduce risk factors, manage stable COPD, prevent and treat acute exacerbations, and manage associated illnesses. The conservative management comprising of antibiotics, inhaled corticosteroids, mucolytics etc. offer promising results in this condition. But tachycardia, glossitis, glaucoma, nausea are some of the common adverse reactions noticed on chronic use of these group of drugs. The contemporary health scenario demands more contribution in this regard from the indigenous system of medicine. In Āyurvedic view, COPD can be considered under the spectrum of Prāṇavaha srotodushti vikaras. The clinical features and etiology mentioned for diseases mentioned in Ayurveda such as Kāsa, Tamaka śvāsa, Rajayakshma etc has similarity with that of COPD. Though COPD cannot be correlated to any single condition of Prāṇavaha sroto duṣti, Tamaka śvāsa can be considered as includes most of the clinical features including cough. When the etiological factors favour, the vitiated and aggravated Kapha dosha blocks the channels of Prāna and Udāna vāta causing the onset and symptoms of the disease.

Elastin-derived peptides favor type 2 innate lymphoid cells in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a condition characterized by chronic airway inflammation and obstruction, primarily caused by tobacco smoking. Although the involvement of immune cells in COPD pathogenesis is well established, the contribution of innate lymphoid cells (ILCs) remains poorly understood. ILCs are a type of innate immune cells that participate in tissue remodeling processes, but their specific role in COPD has not been fully elucidated. During COPD, the breakdown of pulmonary elastin generates elastin peptides that elicit biological activities on immune cells. This study aimed to investigate the presence of ILC in patients with COPD and examine the impact of elastin peptides on their functionality. Our findings revealed an elevated proportion of ILC2 in the peripheral blood of patients with COPD, and a general activation of ILC as indicated by an increase in their cytokine secretion capacity. Notably, our study demonstrated that serum from patients with COPD promotes ILC2 phenotype, likely due to the elevated concentration of IL-5, a cytokine known to favor ILC2 activation. Furthermore, we uncovered that this increase in IL-5 secretion is partially attributed to its secretion by macrophages upon stimulation by elastin peptides, suggesting an indirect role of elastin peptides on ILC in COPD. These findings shed light on the involvement of ILC in COPD and provide insights into the potential interplay between elastin breakdown, immune cells, and disease progression. Further understanding of the mechanisms underlying ILC activation and their interaction with elastin peptides could contribute to the development of novel therapeutic strategies for COPD management.NEW & NOTEWORTHY Elastin-derived peptides, generated following alveolar degradation during emphysema in patients with COPD, are able to influence the response of type 2 innate lymphoid cells. We show that the orientation of innate lymphoid cells in patients with COPD is shifted toward a type 2 profile and that elastin peptides are indirectly participating in that shift through their influence of macrophages, which in turn impact innate lymphoid cells.

Risk of respiratory diseases among hospitalized patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a systemic disorder associated with various metabolic and inflammatory comorbidities. Although HS shares risk factors and pathogenic pathways with various respiratory conditions, few studies have explored the relationship between HS and respiratory disease. This is a cross-sectional, case-control, population-based study that examined the United States National Inpatient Sample database from January 1, 2002, to December 31, 2012. HS was identified using ICD-9-CM codes during hospital admissions. Multivariable logistic regression was used to evaluate for adjusted associations between HS and respiratory diagnoses as compared to matched controls. Twenty-three thousand seven hundred and sixty-seven hospital admissions for HS were compared with 95,068 age- and sex-matched controls. HS patients had significantly higher adjusted odds of asthma (OR: 1.233; 95% CI: [1.170-1.299]; P < 0.001), chronic airway obstruction (OR: 1.532; 95% CI: [1.419-1.651]; P < 0.001), sarcoidosis (OR: 1.601; 95% CI: [1.157-2.214]; P < 0.001), and sleep apnea (OR: 1.274; 95% CI: [1.182-1.374]; P < 0.001). HS is associated with several common forms of respiratory disease. Knowledge of these associations may allow for better recognition of respiratory disease in HS patients.

Pulmonary volumes and signs of chronic airflow limitation in quantitative computed tomography.

Computed tomography (CT) offers pulmonary volumetric quantification but is not commonly used in healthy individuals due to radiation concerns. Chronic airflow limitation (CAL) is one of the diagnostic criteria for chronic obstructive pulmonary disease (COPD), where early diagnosis is important. Our aim was to present reference values for chest CT volumetric and radiodensity measurements and explore their potential in detecting early signs of CAL. From the population-based Swedish CArdioPulmonarybioImage Study (SCAPIS), 294 participants aged 50-64, were categorized into non-CAL (n = 258) and CAL (n = 36) groups based on spirometry. From inspiratory and expiratory CT images we compared lung volumes, mean lung density (MLD), percentage of low attenuation volume (LAV%) and LAV cluster volume between groups, and against reference values from static pulmonary function test (PFT). The CAL group exhibited larger lung volumes, higher LAV%, increased LAV cluster volume and lower MLD compared to the non-CAL group. Lung volumes significantly deviated from PFT values. Expiratory measurements yielded more reliable results for identifying CAL compared to inspiratory. Using a cut-off value of 0.6 for expiratory LAV%, we achieved sensitivity, specificity and positive/negative predictive values of 72%, 85% and 40%/96%, respectively. We present volumetric reference values from inspiratory and expiratory chest CT images for a middle-aged healthy cohort. These results are not directly comparable to those from PFTs. Measures of MLD and LAV can be valuable in the evaluation of suspected CAL. Further validation and refinement are necessary to demonstrate its potential as a decision support tool for early detection of COPD.

Pulmonary hypertension in newly diagnosed obstructive sleep apnea-chronic obstructive pulmonary disease overlap syndrome patients attending a tertiary care centre-a cross-sectional analysis.

Overlap syndrome is the association of obstructive sleep apnea (OSA) with chronic obstructive pulmonary disorder and with other chronic respiratory diseases. Patients with overlap syndrome have a worse prognosis compared with chronic obstructive pulmonary disorder or OSA alone. Additionally, patients with combined chronic obstructive pulmonary disorder and OSA are more likely to develop pulmonary hypertension and right heart failure much earlier than those without overlap. To assess the occurrence of pulmonary hypertension (PH) in newly diagnosed OSA-chronic obstructive pulmonary disorder overlap syndrome patients attending a tertiary care centre. This cross-sectional study was conducted at Department of Pulmonary Medicine, Government Medical College, Kozhikode, Kerala, South India, among patients with OSA above 40years of age who were proactively evaluated to pick out those with undiagnosed overlap. A period of 6months after getting ethical clearance from June 2018 was selected as the study period. Among patients with symptoms suggestive of OSA above 40years of age who gave the informed consent were enrolled after screening with Standard Sleep questionnaires (Berlin questionnaire, STOP BANG and Epworth Sleepiness Scale). Enrolled patients underwent routine spirometry and sleep study using the standard Level 1 overnight polysomnography (Level1 OPSG). Patients were classified in to two groups as OSA patients (group I), having an apnea hypopnea index (AHI) > 5/hr alone and the second group as those OSA patients (group II), with an obstructive spirometry pattern who were the overlap group. Arterial blood gas analysis (a sample of radial arterial blood was drawn with the patient awake and supine, and was analyzed for pH, PaCO2 and PaO2) and echocardiography (ECHO) of the two groups were compared as a non-invasive method to assess pulmonary artery hypertension and results were analyzed in a systematic manner. Among the 84 patients enrolled, 16.7% had overlap syndrome and the rest had OSA alone. Statistically significant higher mean weight and BMI for those with overlap syndrome compared to the OSA group were observed. Mean FVC (forced vital capacity), FEV1 (forced expiratory volume 1s), and FEV1/FVC were lower in those with overlap syndrome compared to OSA group. The mean values of ABG parameters revealed higher PaCO2 and lower PaO2 among the group with overlap syndrome which were statistically significant. However, there was no significant difference in resting room air SaO2 value between the two groups. The mean values of sleep duration and efficiency were significantly lower in those with overlap syndrome with a p value < 0.001. The mean value of arousal and REM (rapid eye movement) sleep percentage were significantly higher among those with overlap syndrome (p < 0.001). Mean value of NREM (non-rapid eye movement) sleep percentage was lower among the group with overlap syndrome compared with the OSA group, and this difference was statistically significant. The mean AHI value of the overlap syndrome group was 39.79 ± 7.54 and this was significantly higher than the OSA group (p < 0.004). Among the 14 patients who had ECHO evidence of pulmonary hypertension, 9 (64.3%) belonged to the overlap group which shows that they are a highly vulnerable group for developing pulmonary hypertension (PH) and requires early detection and more rigorous treatment. This study confirms that OSA patients with modest daytime level of hypoxemia and mild-moderate chronic airflow limitation have a high prevalence of PH. Chronic airway obstruction may be asymptomatic in some subjects and this stresses the necessity of pulmonary function test in OSA.

Abnormal Exertional Breathlessness on Cardiopulmonary Cycle Exercise Testing in Relation to Self-Reported and Physiologic Responses in Chronic Airflow Limitation

Exertional breathlessness is a cardinal symptom of cardiorespiratory disease. How does breathlessness abnormality, graded using normative reference equations during cardiopulmonary exercise testing (CPET), relate to self-reported and physiological responses in people with chronic airflow limitation (CAL)? An analysis was done of people aged≥ 40 years with CAL undergoing CPET in the Canadian Cohort Obstructive Lung Disease study. Breathlessness intensity ratings (Borg CR10 scale [0-10 category-ratio scale for breathlessness intensity rating]) were evaluated in relation to power output (W), rate of oxygen uptake (V˙o2), and minute ventilation (V˙e) at peak exercise, using normative reference equations as follows: (1) probability of breathlessness normality (probability of having an equal or greater Borg CR10 rating among healthy; lower probability reflecting more severe breathlessness) and (2) presence of abnormal breathlessness (rating above the upper limit of normal). Associations with relevant participant-reported and physiologic outcomes were evaluated. We included 330 participants (44%women): mean ± SD age, 64 ± 10 years (range, 40-89 years); FEV1/FVC, 57.3%± 8.2%; FEV1, 75.6%± 17.9%predicted. Abnormally low exercise capacity (peak V˙o2< lower limit of normal) was present in 26%. Relative to peak W, V˙o2, and V˙e, abnormally high breathlessness was present in 26%, 25%, and 18%of participants. For all equations, abnormally high exertional breathlessness was associated with worse lung function, exercise capacity, self-reported symptom burden, physical activity, and health-related quality of life; and greater physiological abnormalities during CPET. Abnormal breathlessness graded using CPET normative reference equations was associated with worse clinical, physiological, and functional outcomes in people with CAL, supporting construct validity of abnormal exertional breathlessness.

Large airway T cells in adults with former bronchopulmonary dysplasia

BackgroundBronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown.ObjectiveTo characterize cellular and T cell profiles in the large airways of young adults with a history of BPD.MethodsForty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry.ResultsThe proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p < 0.001 and p < 0.001). In all adults born prematurely (preterm and BPD), lymphocyte proportion correlated negatively with forced vital capacity (r= -0.324, p = 0.036) and CD8 + T cells correlated with forced expiratory volume in one second, FEV1 (r=-0.448, p = 0.048). Correlation-based network analysis revealed that lung function cluster and BPD-birth cluster were associated with lymphocytes and/or CD4 + and CD8 + T cells. Multivariate regression analysis showed that lymphocyte proportions and BPD severity qualified as independent factors associated with FEV1.ConclusionsThe increased cytotoxic T cells in the large airways in young adults with former BPD, suggest a similar T-cell subset pattern as in the small airways, resembling features of COPD. Our findings strengthen the hypothesis that mechanisms involving adaptive and innate immune responses are involved in the development of airway disease due to preterm birth.

Phenome-wide association study of ovarian cancer identifies common comorbidities and reveals shared genetics with complex diseases and biomarkers.

Ovarian cancer (OC) is commonly diagnosed among older women who have comorbidities. This hypothesis-free phenome-wide association study (PheWAS) aimed to identify comorbidities associated with OC, as well as traits that share a genetic architecture with OC. We used data from 181,203 white British female UK Biobank participants and analysed OC and OC subtype-specific genetic risk scores (OC-GRS) for an association with 889 diseases and 43 other traits. We conducted PheWAS and colocalization analyses for individual variants to identify evidence for shared genetic architecture. The OC-GRS was associated with 10 diseases, and the clear cell OC-GRS was associated with five diseases at the FDR threshold (p = 5.6 × 10-4 ). Mendelian randomizaiton analysis (MR) provided robust evidence for the association of OC with higher risk of "secondary malignant neoplasm of digestive systems" (OR 1.64, 95% CI 1.33, 2.02), "ascites" (1.48, 95% CI 1.17, 1.86), "chronic airway obstruction" (1.17, 95% CI 1.07, 1.29), and "abnormal findings on examination of the lung" (1.51, 95% CI 1.22, 1.87). Analyses of lung spirometry measures provided further support for compromised respiratory function. PheWAS on individual OC variants identified five genetic variants associated with other diseases, and seven variants associated with biomarkers (all, p ≤ 4.5 × 10-8 ). Colocalization analysis identified rs4449583 (from TERT locus) as the shared causal variant for OC and seborrheic keratosis. OC is associated with digestive and respiratory comorbidities. Several variants affecting OC risk were associated with other diseases and biomarkers, with this study identifying a novel genetic locus shared between OC and skin conditions.

Respiratory symptoms, exacerbations and sleep disturbances are more common among participants with asthma and chronic airflow limitation: an epidemiological study in Estonia, Iceland and Sweden

BackgroundChronic airflow limitation (CAL) is a hallmark of chronic obstructive pulmonary disease but is also present in some patients with asthma. We investigated respiratory symptoms, sleep and health status of...