Effect of somatotypes on lung volumes, capacities and respiratory impedance: A pilot study.

BACKGROUND: The current morphological condition of an individual is described by a somatotype, which is a three-number scale. The endomorph, mesomorph and ectomorph components are presented in the same sequence, and each number corresponds to one of the three basic components of body composition. METHODS: We recruited 50 healthy male subjects with a mean age of 24.10 ± 4.55 yrs. Somatotype was determined by the Heath and Carter method. Impulse oscillometry was performed followed by spirometry according to the European Respiratory Society (ERS) or American Thoracic Society (ATS) guidelines. Resistance at 5 Hz (R5) %pred, R20%pred, R5-R20, X5%pred, X20, area of reactance (Ax) and resonant frequency (Fres) were obtained by doing impulse oscillometry. Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio and maximum mid-expiratory flow (MMEF) were assessed by doing spirometry. RESULTS: Endomorphs (0.05 (0.00-0.09) vs 0.01 (0.00-0.04); P < 0.0001) and mesomorphs (0.04 (0.000.09) vs 0.01 (0.00-0.04); P = 0.002) had significantly higher R5-R20 than ectomorphs. Similarly, endomorphs (0.32 (0.07-0.82) vs 0.15 (0.08-0.35); P = 0.001) and mesomorphs (0.28 (0.17-0.64) vs 0.15 (0.08-0.35); P = 0.015) also showed significantly higher Ax than ectomorphs, Fres of endomorphs (15.37 (8.43-21.85) vs 10.08 (8.94-14.30); P < 0.0001) and mesomorphs (14.32 (10.24-20.86) vs 10.08 (8.94-14.30); P < 0.0001) were significantly high than ectomorphs. Moreover, spirometric measures reveal significant variation in which mesomorphs had significantly higher values of % predicted of FVC than ectomorphs (92.49 ± 7.211 vs 83.86 ± 7.861; P = 0.042) and the ratio of FEV1 to FVC was significantly higher in ectomorphs than in endomorphs (89.00 ± 5.80 vs 85.04 ± 5.73; P = 0.03). CONCLUSION: Peripheral airway dysfunction was observed in endomorphs and mesomorphs as compared to ectomorphs. Mesomorphs had a relatively higher FVC that may be due to their greater muscular strength.

Phenotypic Profiling of Immune Cells and Their Mediators in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder and has been proposed to have an imbalance between pro-inflammatory and anti-inflammatory factors. METHODS: This study was conducted on 41 participants {18 COPD patients (smokers, COPD S (n = 9); reformed smokers, COPD RS (n = 9)) and 23 controls (non-smokers, CNS (n = 14); smokers, CS (n = 9))}. Flow cytometry was used to identify circulatory immune cells and correlated with serum cytokines. RESULTS: On comparison, significantly lower frequency of CD3+ T cells were observed in COPD S as compared to CNS (p < 0.01) and CS (p < 0.01); CD4+ T cells were lower in COPD S (p < 0.05), COPD RS (p < 0.05) and CNS (p < 0.01) as compared to CS. CD8+ T cells were elevated in COPD S as compared to CS (p < 0.05). Lower frequency of cDCs were observed in COPD S as compared to CS (p < 0.05) and COPD RS as compared to CNS (p < 0.01) and CS (p < 0.01). Lower frequency of pDCs were observed in COPD RS as compared to COPD S (p < 0.05), CNS (p < 0.05) and CS (p < 0.01). Lower frequency of Tregs was observed in COPD S as compared to CNS (p < 0.05) and CS (p < 0.05). CONCLUSIONS: Characteristic changes observed indicate a significant impact of immune cells in the progression of the disease.

Effect of Obesity on Airway Mechanics.

Background: Obesity is known to induce lung function impairment. Previous studies of decline in lung function associated with obesity are well established. Materials and Methods: In this cross-sectional study, to evaluate the effects of different obesity indices on lung mechanics, healthy subjects (males-23 and females-22) were recruited. Anthropometric parameters like body mass index (BMI), waist circumference (WC), hip circumference (HC) and neck circumference (NC) were measured and waist-hip ratio (WHR) was derived. Spirometry, impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) measurements were performed to assess lung function. Subgroups were divided and analysed. Results: In males, increased WHR is associated with increased total airway resistance (R5). BMI correlates positively with R5, R5% predicted, resistance at 20 Hz (R20) and R20% predicted; likewise, WHR shows a positive correlation with R5. In females, increased WHR has significantly higher R5, R5% predicted, R20, R20% predicted, area of reactance (Ax), resonant frequency (Fres) and decreased reactance at 5 Hz (X5), reactance at 20 Hz (X20), X20% predicted. The female group with higher WC shows significantly increased R5, R5% predicted, R20, R20% predicted, Ax, Fres and lower fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), X5, X20, X20% predicted. The group with higher NC has a lower FEV1/FVC ratio. WHR positively correlated with R5% predicted and Fres while WC correlated positively with R5, R5% predicted, Ax and Fres; same way, NC with X5% predicted. Conclusion: Obesity/overweight causes significant changes in lung volumes, capacity and airway mechanics, Higher WC and WHR are associated with significant changes in lung mechanics, which are more prominent in females than in males. NC is not associated with changes in lung mechanics.

Comparative study of the effect of N95 facemask and Powered Air-purifying Respirator (2 fans, N95 filter) on cardiovascular parameters of healthy individuals during exercise.

N95 masks filter 95% of the small particles and respiratory droplets (>0.3 µm diameter). Therefore, they are widely used both by general public and health workers during pandemic. When physical activity or exercise is performed wearing N95 mask, it induces hypercapnic environment. The heat burden is also increased leading to discomfort and reduced compliance. This study was done to compare physiological effects and subjective perceptions while wearing N95 mask and powered air-purifying respirator (PAPR) (2 fans, N95 filter) during incremental exercise. ECG, respiratory movement, SpO2, temperature inside the mask were recorded and perception of discomfort was also assessed. Heart rate variability (HRV) values during baseline were within normal limits in both the mask conditions signifying that cardiac autonomic tone is comparable. During incremental exercise, fall in SpO2 was significantly lesser in PAPR as compared to N95 mask at 60-70% and 70-80% of maximum achievable heart rate. The temperatures inside both the mask conditions were significantly higher than ambient temperature. The scores of humid, hot, breath resistance and fatigue were significantly lower in PAPR than N95 mask. In conditions where prolonged use of mask is required with strenuous physical exertion or exercise, PAPR could be preferred over N95 mask.

Respiratory Dysfunction in Parkinson's Disease: Relation with Dysautonomia.

Background: Parkinson's disease (PD) is a neurodegenerative disease perceived as a motor disorder. It is most commonly associated with autonomic dysfunction, affecting multiple systems. This altered autonomic control might be reflected by a parallel change in the airway caliber of these patients. Aim: To correlate the pulmonary impairment in patients with Parkinson's disease with the underlying dysautonomia. Materials and Methods: A total of 30 patients with Parkinson's disease participated in the study. Heart rate (HR) variability was recorded for 5 min to assess the autonomic dysfunction, followed by impulse oscillometry (IOS) and spirometry. IOS being an effort independent technique uses sound waves at different frequencies (5-25 Hz) to measure the airway impedance. Results: There was a significant decrease in SDSD (6.60 (10.18-6.01) vs. 12.22 (13.95-11.30); P = 0.04), RMSSD (6.59 (10.17-5.50) vs. 12.20 (13.93-11.28); P = 0.04), and total power (315.8 (506.3-120.7) vs. 771.3 (799.0-643.6); P = 0.04) in stage II as compared to stage I. Resistance at 20 Hz (R20) was found to be positively correlated with SDSD (r = 0.40, P = 0.04), RMSSD (r = 0.40, P = 0.04), and HF (r = 0.41, P = 0.03). Conclusion: Amongst the PD population, any changes in the parasympathetic component (responsible for bronchoconstriction) due to the underlying dysautonomia might be reflected as increased airway resistance in the pulmonary system.

Pulmonary Functions and Inflammatory Biomarkers in Post-Pulmonary Tuberculosis Sequelae.

BACKGROUND: Post-tuberculosis (TB) sequelae is a commonly encountered clinical entity, especially in high TB burden countries. This may represent chronic anatomic sequelae of previously treated TB, with frequent symptomatic presentation. This pilot study was aimed to investigate the pulmonary functions and systemic inflammatory markers in patients with post-TB sequelae (PTBS) and to compare them with post-TB without sequelae (PTBWS) participants and healthy controls. METHODS: A total of 30 participants were enrolled, PTBS (n=10), PTBWS (n=10), and healthy controls (n=10). Pulmonary function tests included spirometry and measurement of airway impedance by impulse oscillometry. Serum levels of matrix metalloproteinase (MMP)-1, transforming growth factor-ß, and interferon-γ were estimated. RESULTS: Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC, and peak expiratory flow were significantly lower in PTBS as compared to controls. SVC and FEV1 were significantly less in PTBS as compared to PTBWS. Total airway impedance (Z5), total airway resistance (R5), central airway resistance (R20), area of reactance (Ax), and resonant frequency (Fres) were significantly higher and respiratory reactance at 5 and 20 Hz (X5, X20) were significantly lower in PTBS as compared to PTBWS. Spirometry parameters correlated with impulse oscillometry parameters in PTBS. Serum MMP-1 level was significantly higher in PTBS as compared to other groups. CONCLUSION: Significant pulmonary function impairment was observed in PTBS, and raised serum MMP-1 levels compared with PTBWS and healthy controls. Follow-up pulmonary function testing is recommended after treatment of TB for early diagnosis and treatment of PTBS.

Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients.

RATIONALE: Smoking is the primary cause of chronic obstructive pulmonary disease (COPD); however, only 10-20% of smokers develop the disease suggesting possible genomic association in the causation of the disease. In the present study, we aimed to explore the whole genome transcriptomics of blood monocytes from COPD smokers (COPD-S), COPD Ex-smokers (COPD-ExS), Control smokers (CS), and Control Never-smokers (CNS) to understand the differential effects of smoking, COPD and that of smoking cessation. METHODS: Exploratory analyses in form of principal component analysis (PCA) and hierarchical component analysis (uHCA) were performed to evaluate the similarity in gene expression patterns, while differential expression analyses of different supervised groups of smokers and never smokers were performed to study the differential effect of smoking, COPD and smoking cessation. Differentially expressed genes among groups were subjected to post-hoc enrichment analysis. Candidate genes were subjected to external validation by quantitative RT-PCR experiments. RESULTS: CNS made a cluster completely segregated from the other three subgroups (CS, COPDS and COPD-ExS). About 550, 8 and 5 genes showed differential expression, respectively, between CNS and CS, between CS and COPD-S, and between COPD-S and COPD-ExS. Apoptosis, immune response, cell adhesion, and inflammation were the top process networks identified in enrichment analysis. Two candidate genes (CASP9 and TNFRSF1A) found to be integral to several pathways in enrichment analysis were validated in an external validation experiment. CONCLUSION: Control never smokers had formed a cluster distinctively separated from all smokers (COPDS, COPD-ExS, and CS), while amongst all smokers, control smokers had aggregated in a separate cluster. Smoking cessation appeared beneficial if started at an early stage as many genes altered due to smoking started reverting towards the baseline, whereas only a few COPD-related genes showed reversal after smoking cessation.

Impulse Oscillometry as a measure of airway dysfunction in Sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic inflammatory granulomatous disease which commonly affects intrathoracic lymph nodes, lung parenchyma and airways. OBJECTIVES: To measure respiratory impedance using Impulse Oscillometry (IOS) in patients with pulmonary sarcoidosis and compare the parameters with healthy controls. METHODS: Patients diagnosed with sarcoidosis (n=28); and age and gender matched healthy controls (n=17) were recruited. Lung volumes and capacities were measured by spirometry and respiratory system impedance was assessed using Impulse Oscillometry System (IOS). Measurements were performed before and 15 minutes after inhalation of a short acting bronchodilator. The IOS and spirometric parameters were compared between two groups and correlated. ROC curve analysis was also performed to identify the IOS parameters which can discriminate between sarcoidosis and healthy controls. RESULTS: Resistance at 5 and 20 Hz (R5 and R20), small airway resistance (R5-R20), resonant frequency (FRes) and area of reactance (AX) were significantly higher in Sarcoidosis subjects compared with controls. Reactance at 5 and 20 Hz (X5 and X20) were significantly lower in sarcoidosis. FEV1 (% predicted) and FVC (% predicted) were significantly lower in patients with sarcoidosis while FEV1/FVC ratio and peak expiratory flow rate (PEF) values were comparable. Post bronchodilator inhalation, there was improvement in airway resistance and reactance, but no significant changes observed in spirometric parameters. R5, X5 and R5-R20 are promising parameters to discriminate sarcoidosis from healthy controls. CONCLUSION: Increased airway resistance is a better indicator of airway involvement than airflow limitation by spirometry in pulmonary sarcoidosis.

Exhaled Breath Temperature and Systemic Biomarkers for Assessment of Airway Inflammation in Asthmatics.

OBJECTIVES: Asthma is characterised by chronic airway inflammation and remodelling. Inflammation may alter the thermal balance of the affected tissues secondary to changes in the blood flow. Measurement of exhaled breath temperature (EBT) is a simple, safe and non-invasive technique to detect airway inflammation. The objective of this study was to measure EBT in asthma patients and compare it with healthy controls and also to correlate it with serum biomarkers of inflammation and remodelling. METHODS: 24 male asthma patients and 23 age and gender matched healthy controls were recruited in the study. EBT and core body temperature were recorded followed by spirometry to measure forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR). Serum levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were quantified by ELISA. RESULTS: Asthmatics had significantly lower FEV1% predicted compared to healthy subjects. EBT in asthma patients was significantly higher as compared to healthy controls while rate of rise of EBT was not significantly different. Serum biomarker of inflammation i.e. IL-6 and of tissue remodelling i.e. VEGF, MMP-9 and TIMP-1 were significantly raised in asthma patients while the ratio of MMP-9/TIMP-1 was comparable between two groups. But no correlation was observed between EBT and serum biomarkers. CONCLUSION: EBT may be used as an adjunct tool for non-invasive assessment of airway inflammation and remodelling in asthma patients.

Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development.

Morbidity, mortality and economic burden caused by chronic obstructive pulmonary disease (COPD) is a significant global concern. Surprisingly, COPD is already the third leading cause of death worldwide, something that WHO had not predicted to occur until 2030. It is characterized by persistent respiratory symptoms and airway limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases. Neutrophil is one of the key infiltrated innate immune cells in the lung during the pathogenesis of COPD. Neutrophils during pathogenic attack or injury decide to undergo for a suicidal death by releasing decondensed chromatin entangled with antimicrobial peptides to trap and ensnare pathogens. Casting neutrophil extracellular traps (NETs) has been widely demonstrated to be an effective mechanism against invading microorganisms thus controlling overwhelming infections. However, aberrant and massive NETs formation has been reported in several pulmonary diseases, including chronic obstructive pulmonary disease. Moreover, NETs can directly induce epithelial and endothelial cell death resulting in impairing pulmonary function and accelerating the progression of the disease. Therefore, understanding the regulatory mechanism of NET formation is the need of the hour in order to use NETs for beneficial purpose and controlling their involvement in disease exacerbation. For example, DNA neutralization of NET proteins using protease inhibitors and disintegration with recombinant human DNase would be helpful in controlling excess NETs. Targeting CXC chemokine receptor 2 (CXCR2) would also reduce neutrophilic inflammation, mucus production and neutrophil-proteinase mediated tissue destruction in lung. In this review, we discuss the interplay of NETs in the development and pathophysiology of COPD and how these NETs associated therapies could be leveraged to disrupt NETopathic inflammation as observed in COPD, for better management of the disease.

Contribution of systemic vascular reactivity to variability in pulse volume amplitude response during reactive hyperemia.

PURPOSE: The aim of the present study was to investigate why the magnitude of reactive hyperemia (RH) observed by pulse volume amplitude (PVA) after arm occlusion differs greatly among study subjects. METHODS: Healthy subjects (n = 12) in the age range of 22-30 years participated in this study. Vascular reactivity was assessed by measuring the changes in finger PVA simultaneously in the test (occluded arm) and control arm (contralateral non-occluded arm) using two separate Photoplethysmographic sensors. Short-term HRV was computed from simultaneously acquired lead II ECG signal to monitor the changes in cardiac sympathetic nervous activity. RESULTS: The observed coefficient of variation for inter-subject variability in PVA response in test arm during second minute of RH was 115.3%. In the control arm, significantly reduced PVA was observed during the period of occlusion as well as RH. This observation was corroborated by simultaneously acquired short-term HRV which showed a significant rise in total power (p value < 0.005) and low-frequency (LF) power (p value < 0.05) during release of occlusion when compared to the baseline. A significant positive correlation (Spearman r = 0.33; p = 0.02) was observed between % change in PVA in the control arm and in the test arm for first 3 min of RH. CONCLUSIONS: Sympathetic activation possibly plays an important role in mediating the inter-subject variability of vascular responses during reactive hyperemia which warrants simultaneous recording of both the test and the control arm responses during RH to accurately assess endothelial function.

Postural variation of pulmonary diffusing capacity as a marker of lung microangiopathy in Indian patients with type 2 diabetes mellitus.

INTRODUCTION: Diabetes mellitus (DM) is characterized by the presence of chronic hyperglycemia and formation of advanced glycation end products (AGEs). Interaction between AGE and its receptor leads to endothelial damage and microangiopathy. This study was undertaken to investigate the possibility of using a postural variation of diffusing capacity as an early marker of lung microangiopathy and its correlation with the level of adhesion molecules, HbA1c, duration of diabetes, and insulin resistance in type 2 DM (T2DM) patients with and without microangiopathy. MATERIALS AND METHODS: Forty patients having T2DM without any microangiopathy (n = 20) as well as with microangiopathy (n = 20), and 22 age and sex matched healthy controls were enrolled in this cross-sectional study. Measurement of lung volumes and capacities were done. DLco was measured in sitting and supine position. Levels of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, fasting glucose, and insulin were estimated in plasma of the patients and compared with controls. RESULTS: Restrictive type of ventilatory change was observed in DM patients. Diffusing capacity (% predicted) in the supine position (P < 0.0001), postural change in DLco (P < 0.0001), and coefficient of diffusion were significantly less in DM patients as compared to controls. Plasma levels of VCAM-1 were significantly higher in DM patients without microangiopathy and negatively correlated (r = -0.4054, P = 0.0094) with Δ DLco in all diabetic subjects. All patients had significantly higher insulin resistance. CONCLUSION: Lack of postural increase in diffusing capacity in type 2 diabetic patients along with increased VCAM-1 levels could reflect the presence of an early microangiopathy of the small pulmonary vessels.

Slower rise of exhaled breath temperature in cystic fibrosis.

OBJECTIVE: To measure exhaled breath temperature in patients with cystic fibrosis. METHODS: 17 patients (6-18 years) with cystic fibrosis and 15 age- and gender-matched healthy controls were recruited in this cross sectional study. Exhaled breath temperature was measured in subjects recruited in both the groups with a device X-halo and analyzed as plateau temperature achieved and rate of temperature rise. RESULTS: Patients with cystic fibrosis showed no significant difference in plateau temperature [34.4(32.3-34.6) versus 33.9 (33.0-34.4)oC; P=0.35] while mean (SEM.) rate of temperature rise was significantly less in patients [0.09 (0.01) versus 0.14 (0.02) ƼC/s ; P=0.04] as compared to controls. CONCLUSIONS: There was a slower rise of exhaled breath temperature in patients with cystic fibrosis whereas plateau temperature was not significantly different from controls.

Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process.