Mangiferin attenuates cigarette smoke-induced chronic obstructive pulmonary disease in male albino rats.

We analyzed the ability of mangiferin to suppress cigarette smoke-induced chronic obstructive pulmonary disease. Control rats showed a marked decrease in the ratio of the forced expiratory volume at 0.1 s to forced vital capacity. The decreases in the peak expiratory flow and maximal mid-expiratory flow indicated airway remodeling and enlargement. The expression levels of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase, nuclear factor erythroid 2-related factor 2, and activating transcription factor 4 were increased in the control rats. The levels of oxidative stress, malondialdehyde, and reactive oxygen species peaked after 24 weeks, whereas the SOD and HO-1 levels and the total antioxidant capacity were reduced in control rats. Mangiferin restored the levels of reactive oxygen species, malondialdehyde, SOD, HO-1, and T-AOC to near normal. Increased numbers of infiltrating inflammatory cells were observed in control rats but were significantly reduced by mangiferin. In addition, edema and airway inflammation were reduced by mangiferin.

Reduced pulmonary function, low-grade inflammation and increased risk of total and cardiovascular mortality in a general adult population: Prospective results from the Moli-sani study.

AIM: to investigate the relation of pulmonary function impairment with mortality and the possible mediation by low-grade inflammation in a general adult population. METHODS: A prospective investigation was conducted on 14,503 individuals from the Moli-sani study (apparently free from lung disease and acute inflammatory status at baseline; 2005-2010). The 2012 Global Lung Function Initiative percent predicted (% pred) value of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75) and FEV1 quotient (FEV1Q) index were used. C-reactive protein and blood cell counts were measured and a score of subclinical inflammation (INFLA-score) was calculated. RESULTS: Over a median follow-up of 8.6y, 503 deaths (28.9% cardiovascular) were ascertained. Total mortality increased by 19% for each decrease in 1 standard deviation of FEV1% pred or FVC% pred (Hazard Ratio:1.19; 95% CI:1.11-1.28 and 1.19; 1.10-1.28, respectively). Comparable findings for FEV1Q (1.30; 1.15-1.47) were observed. A statistically significant increased risk in cardiovascular mortality of 23%, 32% and 49% was observed for 1 standard deviation decrease of FEV1% pred, FVC% pred and FEV1Q, respectively. INFLA-score mediated the association of FEV1% pred and FEV1Q with cardiovascular mortality by 22.3% and 20.1%, respectively. Subjects with FEV1, FVC lower than normal limit showed increased risk both in total and cardiovascular mortality. Abnormal FEF25-75 values were associated with 33% (1.33; 1.02-1.74) total mortality risk. CONCLUSIONS: Obstructive lung function impairment was associated with decreased survival. Low-grade inflammation mainly mediated the association of FEV1 with cardiovascular mortality.

Effect of Pod e-Cigarettes vs Cigarettes on Carcinogen Exposure Among African American and Latinx Smokers: A Randomized Clinical Trial.

Importance: Fourth-generation nicotine salt pod system (NSPS) electronic cigarettes (e-cigarettes) are the leading class of e-cigarettes. They contain high nicotine concentrations, which may facilitate switching among smokers, but could also lead to increased exposure to nicotine and biomarkers of potential harm. African American and Latinx smokers experience significant tobacco-related health disparities. The potential of NSPS e-cigarettes to reduce smoking-related harm among these groups is unknown. Objective: To compare the harm reduction potential of NSPS e-cigarette vs combustible cigarettes. Design, Setting, and Participants: This unblinded randomized clinical trial compared 6 weeks of e-cigarette use vs cigarettes as usual from to 2018 to 2019 among smokers in the San Diego, California, and Kansas City, Missouri, areas. Participants included African American and Latinx adult combustible cigarette smokers who smoked at least 5 cigarettes/d on at least 25 of the past 30 days for at least 6 months and were interested in switching to e-cigarettes. Data were analyzed from September 18, 2019, to September 4, 2020. Interventions: 6 weeks of e-cigarette use in a choice of pod flavors (5% nicotine) along with brief education, training, and action planning to completely switch to e-cigarettes from combustible cigarettes. The control group smoked combustible cigarettes as usual. Main Outcomes and Measures: The primary outcome was reduction in urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentration at week 6. Secondary outcomes were change in urinary cotinine, expired carbon monoxide (CO), respiratory symptoms, lung function, blood pressure, past 7-day consumption of combustible cigarettes, and switching rates (e-cigarette group only) at weeks 2 and 6. Results: This study included 186 participants, including 92 African American participants and 94 Latinx participants. The mean (SD) age was 43.3 (12.5) years, and 75 (40.3%) were women. Participants smoked a mean (SD) of 12.1 (7.2) cigarettes/d on 6.8 (0.6) d/wk at baseline. A total of 125 participants were randomized to the e-cigarette group and 61 were randomized to the control group. At baseline, median (interquartile range) NNAL was 124 (45-197) pg/mL in the e-cigarette group and 88 (58-197) pg/mL in the control group. At week 6, the e-cigarette group had significantly greater reductions in NNAL (relative risk [RR], 0.36 [95% CI, 0.23-0.54]; P < .001), CO (RR, 0.53 [95% CI, 0.42-0.68]; P < .001), respiratory symptoms (RR, 0.63 [95% CI, 0.47-0.85]; P = .002), and number of cigarettes smoked in the past 7 days among those still smoking (RR, 0.30 [95% CI, 0.20-0.43]; P < .001) than the control group and maintained their cotinine levels (RR, 0.80 [95% CI, 0.58-1.10]; P = .17). Lung function and diastolic and systolic blood pressure remained unchanged and did not differ between groups. For participants randomized to receive e-cigarettes, 32 participants (28.1%) were exclusively using e-cigarettes at week 6, while 66 participants (57.9%) were dual using and 16 participants (14%) resumed exclusively using cigarettes. Conclusions and Relevance: These findings suggest that e-cigarettes may be an inclusive harm reduction strategy for African American and Latinx smokers. Trial Registration: ClinicalTrials.gov Identifier: NCT03511001.

Association of Neutrophil to Lymphocyte Ratio With Pulmonary Function in a 30-Year Longitudinal Study of US Veterans.

Importance: Chronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood. Objective: To explore the associations of NLR with lung function decline and COPD risks. Design, Setting, and Participants: This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018. A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD. Data were analyzed from September 2019 to January 2020. Exposures: The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit. The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits. Main Outcomes and Measures: The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria. Both outcomes were measured as each visit. Results: Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF. Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function. Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline. Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function. Conclusions and Relevance: These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.

Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma.

BACKGROUND: The humanized monoclonal antibody benralizumab targets the α subunit of the interleukin-5 (IL-5) receptor and the FcγRIIIa receptor expressed by natural killer cells. Through this dual mechanism of action, benralizumab neutralizes the pro-eosinophil functions of IL-5 and promotes eosinophil apoptosis. OBJECTIVES AND METHODS: The present real-life study aimed to evaluate, in 22 allergic patients with severe eosinophilic asthma, the effects of benralizumab on asthma exacerbations and lung hyperinflation. RESULTS: In this regard here we show that, after 24 weeks of add-on treatment, benralizumab completely depleted peripheral blood eosinophils (from 810 to 0 cells/µL; p < 0.0001), and significantly decreased both asthma exacerbation number (from 4 to 0; p < 0.0001) and residual volume (from 2720 to 2300 mL; p < 0.01). Moreover, at the same time point (24 weeks) benralizumab also increased pre-bronchodilator FEV1 (from 1295 to 1985 mL; p < 0.0001), FVC (from 2390 to 2974 mL; p < 0.0001), FEF25-75 (from 0.6 to 1.42 L/sec; p < 0.0001), IC (from 1940 to 2460 mL; not significant), and ACT score (from 14.73 to 22.95; p < 0.0001), as well as reduced prednisone intake (from 25 to 0 mg; p < 0.0001). CONCLUSION: In conclusion, our results suggest that via its anti-eosinophil actions benralizumab improved airflow limitation, lung hyperinflation, and respiratory symptoms, as well as lowered asthma exacerbation rate and abrogated OCS consumption in most patients.

Biomarkers of aging and lung function in the normative aging study.

Elderly individuals who are never smokers but have the same height and chronological age can have substantial differences in lung function. The underlying biological mechanisms are unclear. To evaluate the associations of different biomarkers of aging (BoA) and lung function, we performed a repeated-measures analysis in the Normative Aging Study using linear mixed-effect models. We generated GrimAgeAccel, PhenoAgeAccel, extrinsic and intrinsic epigenetic age acceleration using a publically available online calculator. We calculated Zhang's DNAmRiskScore based on 10 CpGs. We measured telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) using quantitative real-time polymerase chain reaction. A pulmonary function test was performed measuring forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC), FEV1, and maximum mid-expiratory flow (MMEF). Epigenetic-based BoA were associated with lower lung function. For example, a one-year increase in GrimAgeAccel was associated with a 13.64 mL [95% confidence interval (CI), 5.11 to 22.16] decline in FEV1; a 0.2 increase in Zhang's DNAmRiskScore was associated with a 0.009 L/s (0.005 to 0.013) reduction in MMEF. No association was found between TL/mtDNA-CN and lung function. Overall, this paper shows that epigenetics might be a potential mechanism underlying pulmonary dysfunction in the elderly.

Respiratory and Cardiovascular Outcomes in Survivors of Extremely Preterm Birth at 19 Years.

Rationale: Growth and development during adolescence may modify the respiratory and vascular differences seen among extremely preterm (EP) individuals in childhood and early adolescence.Objectives: To assess the trajectory of respiratory and cardiovascular outcomes during transition to adulthood in a national longitudinal cohort study of births before 26 weeks of gestation in the United Kingdom and Ireland.Methods: A total of 129 EP participants and 65 control subjects attended for a center-based evaluation at 19 years of age. Standardized measures of spirometry, hemodynamics, functional capacity, and markers of inflammation were obtained from EP subjects with and without neonatal bronchopulmonary dysplasia and term-born control subjects at 19 years of age and compared with previous assessments.Measurements and Main Results: Compared with the control group, the EP group was significantly impaired on all spirometric parameters (mean FEV1z-score, -1.08 SD [95% confidence interval, -1.40 to -0.77]) and had lower fractional exhaled nitric oxide concentrations (13.9 vs. 24.4 ppb; P < 0.001) despite a higher proportion with bronchodilator reversibility (27% vs. 6%). The EP group had significantly impaired exercise capacity. All respiratory parameters were worse after neonatal bronchopulmonary dysplasia, and respiratory function differences were similar at 11 and 19 years. The augmentation index was 6% higher in the EP group and associated with increased total peripheral resistance (difference in means, 96.4 [95% confidence interval, 26.6-166.2] dyne/s/cm-5) and elevation in central, but not peripheral, blood pressure. Central systolic and diastolic blood pressures increased more quickly during adolescence in the EP group than in the control group.Conclusions: Clinicians should address both cardiovascular and respiratory risks in adult survivors of extremely preterm birth.

Acute changes in lung function following controlled exposure to cookstove air pollution in the subclinical tests of volunteers exposed to smoke (STOVES) study.

Background: Exposure to household air pollution generated as a result of cooking and heating is a leading contributor to global disease. The effects of cookstove-generated air pollution on adult lung function, however, remain uncertain.Objectives: We investigated acute responses in lung function following controlled exposures to cookstove-generated air pollution.Methods: We recruited 48 healthy adult volunteers to undergo six two-hour treatments: a filtered-air control and emissions from five different stoves with fine particulate matter (PM2.5) targets from 10 to 500 µg/m3. Spirometry was conducted prior to exposure and immediately, and three and 24 h post-exposure. Mixed-effect models were used to estimate differences in post-exposure lung function for stove treatments versus control.Results: Immediately post-exposure, lung function was lower compared to the control for the three highest PM2.5-level stoves. The largest differences were for the fan rocket stove (target 250 µg/m3; forced vital capacity (FVC): -60 mL, 95% confidence interval (95% CI) -135, 15; forced expiratory volume (FEV1): -51 mL, 95% CI -117, 16; mid-expiratory flow (FEF25-75): -116 mL/s, 95% CI -239, 8). At 3 h post-exposure, lung function was lower compared to the control for all stove treatments; effects were of similar magnitude for all stoves. At 24 h post-exposure, results were consistent with a null association for FVC and FEV1; FEF25-75 was lower relative to the control for the gasifier, fan rocket, and three stone fire.Conclusions: Patterns suggesting short-term decreases in lung function follow from exposure to cookstove air pollution even for stove exposures with low PM2.5 levels.

Optimization of Nebulized Budesonide in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background: Clinical studies have suggested nebulized budesonide (NB) as an alternative to systemic corticosteroids for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the optimal budesonide dose for AECOPD remains unclear. Objectives: To compare the efficacy and safety of different doses of NB in the management of AECOPD. Patients and Methods: A total of 321 AECOPD patients with moderate-to-severe exacerbation were randomly divided into three groups and treated with NB. The low dose group (L) was given 4 mg/day (n=95, 1 mg Q6h), while high-dose group 1 (H1, n=111, 2 mg Q6h) and high-dose group 2 (H2, n=115, 4 mg Q12h) were given 8 mg/day. Patients also received routine treatment including oxygen therapy, expectorant, nebulization bronchodilators, antibiotics, and fluid rehydration. The COPD assessment test (CAT), lung function, and artery blood gas were evaluated before and after 3 hrs and 5 days of treatment. In addition, hospital stay, frequency of acute exacerbations within 3 months of discharge, and adverse events during treatment were compared. Results: H1 and H2 showed improved spirograms and CAT score faster than L. In H2, forced expiratory volume in 1 s (FEV1%) at 3 hrs and FEV1%, forced expiratory flow after 50% of the forced vital capacity has been exhaled (FEF50%), mean forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) and CAT score at 5 days were significantly improved compared to L. FEV1% improved most in H2, moderately in H1, and least in L, with significant differences between groups at 5 days. No differences between groups were observed in adverse effects, hospital stay, and frequency of exacerbations within 3 months of discharge. Conclusion: Compared to the conventional dose (4 mg/day), a high dose (8 mg/day) of NB improved pulmonary function and symptoms more effectively in the early treatment of AECOPD, especially when given as 4 mg twice daily.

The Effect of Vitamin D Supplementation on Clinical Outcomes of Asthmatic Children with Vitamin D Insufficiency.

BACKGROUND: The extensive impacts of vitamin D on the immune system has gathered the attention of scholars in last years. In this regard, studies about vitamin D and incidence of asthma have showed various results. The aim of this study was to evaluate the effect of vitamin D supplements on clinical outcomes in asthmatic children with vitamin D insufficiency. MATERIALS & METHODS: This before-after interventional study was conducted on all asthmatic children who attended the Be'sat Hospital, Iran. Serum levels of 25(OH)D, asthma severity and pulmonary function tests before and after therapeutic prescription of vitamin D were evaluated. Serum levels of 25(OH)D were measured by enzyme-linked immunosorbent assay. RESULTS: The mean age of the samples was 10.69±9.78 years and 39 subjects (57.4%) were male. The primary mean level of serum 25(OH)D (18.21±8.22, ng/mL) has significantly (p<0.05) increased after treatment (35.45±9.35, ng/mL). Also, asthma severity, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC indicators were significantly (p<0.05) increased after treatment. CONCLUSION: We can conclude that therapeutic prescription of vitamin D is very effective in improving the clinical status of asthmatic children.

Use of FEF25-75% to Guide IgG Dosing to Protect Pulmonary Function in CVID.

Immunoglobulin replacement therapy (IGRT) can protect against lung function decline in CVID. We tested whether increasing IgG dosage was beneficial in patients who exhibited a decline in forced expiratory flow at 25-75% (FEF25-75%) even though they were receiving IgG doses within the therapeutic range. Of 189 CVID patients seen over 12 years, 38 patients met inclusion criteria, were seen on ≥ 3 visits, and demonstrated a ≥ 10% decrease in FEF25-75% from visits 1 to 2. FEF25-75%, forced expiratory flow at 1 s (FEV1), and FEV1/FVC at visit 3 were compared among those with non-dose adjustment (non-DA) versus additional IgG dose adjustment (DA). Three FEF25-75% tiers were identified: top (> 80% predicted), middle (50-80%), and bottom (< 50%). DA and non-DA groups did not differ in clinical infections or bronchodilator use, although the non-DA group tended to use more antibiotics. In the top, normal tier, FEF25-75% increased in DA, but the change did not achieve statistical significance. In the middle moderate obstruction tier, visit 3 FEF25-75% increased among DA but not non-DA sets (11.8 ± 12.4%, p = 0.003 vs. 0.3 ± 9.9%, p = 0.94). Improvement in FEV1/FVC at visit 3 was also significant among DA vs. non-DA (7.2 ± 12.4%, p = 0.04 vs. - 0.2 ± 2.7%, p = 0.85). In the bottom, severe tier, FEF25-75% was unchanged in DA (- 0.5 ± 5.2%, p = 0.79), but increased in non-DA (5.1 ± 5.2%, p = 0.02). Among IGRT CVID patients with moderate but not severe obstruction as assessed by spirometry, increasing IgG dosage led to an increase in FEF25-75% and FEV1/FVC.

Bronchodilatory effects of B-type natriuretic peptide in acute asthma attacks: a randomized controlled clinical trial.

INTRODUCTION: B-type natriuretic peptide (BNP) regulates different physiological processes such as blood pressure, cardiac growth, and neural and skeletal development. Thus, the aim of this study w as to evaluate the effect of BNP in the treatment of acute asthma attacks. MATERIAL AND METHODS: In this randomized clinical trial, patients with acute asthma attacks were enrolled. The patients were divided randomly into two groups. Patients in the interventional group received BNP via intravenous infusion. Two µg/kg of BNP was injected as a bolus in 60 seconds. Then, infusion of BNP immediately began and was given in 0.01, 0.02, and 0.03 µg/kg/min doses every 30 minutes for the first 1.5 hours. The patients in the control group received nebulized salbutamol. Afterwards, peak flow meter findings, hemodynamic parameters, and estimation of the clinical severity of asthma in both groups were checked every 30 minutes. RESULTS: In total, 40 patients were included in this study. The values of PEFR in the 60th and 90th minutes in the control group were lower than those in the interventional group. In the 60th minute, the mean of PEFR was 377.3 in the BNP group but 335.95 in the control group (P = 0.049). Moreover, this difference remained significant in the 90th minute (P = 0.021). However, forced expiratory volume in one second (FEV1) did not differ between the groups at any time (p > 0.05). CONCLUSION: Although a large experimental study is needed to verify our hypothesis, it seems that BNP might be a therapeutic option in asthma exacerbations, particularly in those with b2 agonist receptor polymorphism.

Abnormal Lung Clearance Index in Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Children with Otherwise Normal FEV1.

In preschool children with cystic fibrosis (CF), lung clearance index (LCI) is a sensitive test to detect early lung disease. Some children with CF screen positive, inconclusive diagnosis (CFSPID) may in time develop clinical features of CF. LCI has not been studied in CFSPID children. LCI and spirometry were performed in preschool age children with CF, CFSPID, and non-CF healthy controls (HCs) during two visits. Fifty-four preschool age children (HC n = 18, CFSPID n = 17, and CF n = 19) were tested. Mean LCI from the CFSPID group was not statistically different from HC (p = 0.49), but significantly different when compared to CF (p = 0.04). LCI was abnormal in 2 CFSPID children who carried potentially deleterious CFTR variants. Mean forced expiratory volume in 1 s (FEV1) was not statistically different between CFSPID and CF (p = 0.26). LCI can potentially detect early lung disease in CFSPID individuals as part of assessing their risk for reclassification to CF diagnosis.

Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients.

BACKGROUND: Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. METHODS: In this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC <80% - VR >100% - FEF 25-75%<60%); 2) non-small airways phenotype (NSAP) group: non-smokers, without air trapping (FVC ≥80% - VR ≤ 100% - FEF 25-75%≥60%). We later proceeded in both groups with a step up in therapy with high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate (BDP/FF) (200/6 µg) in fixed dose to achieve a better control and followed patients for 6 months. RESULTS: Treatment with extrafine BDP/FF(200/6 µg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. CONCLUSIONS: Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 µg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP.

The Effects of Rare SERPINA1 Variants on Lung Function and Emphysema in SPIROMICS.

Rationale: The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, SERPINA1 (serpin peptidase inhibitor, clade A, member 1), in determining chronic obstructive pulmonary disease risk and severity is controversial.Objectives: To comprehensively evaluate the effects of rare SERPINA1 variants on lung function and emphysema phenotypes in subjects with significant tobacco smoke exposure using deep gene resequencing and alpha-1 antitrypsin concentrations.Methods: DNA samples from 1,693 non-Hispanic white individuals, 385 African Americans, and 90 Hispanics with ≥20 pack-years smoking were resequenced for the identification of rare variants (allele frequency < 0.05) in 16.9 kB of SERPINA1.Measurements and Main Results: White PI Z heterozygotes confirmed by sequencing (MZ; n = 74) had lower post-bronchodilator FEV1 (P = 0.007), FEV1/FVC (P = 0.003), and greater computed tomography-based emphysema (P = 0.02) compared with 1,411 white individuals without PI Z, S, or additional rare variants denoted as VR. PI Z-containing compound heterozygotes (ZS/ZVR; n = 7) had lower FEV1/FVC (P = 0.02) and forced expiratory flow, midexpiratory phase (P = 0.009). Nineteen white heterozygotes for five non-S/Z coding variants associated with lower alpha-1 antitrypsin had greater computed tomography-based emphysema compared with those without rare variants. In African Americans, a 5' untranslated region insertion (rs568223361) was associated with lower alpha-1 antitrypsin and functional small airway disease (P = 0.007).Conclusions: In this integrative deep sequencing study of SERPINA1 with alpha-1 antitrypsin concentrations in a heavy smoker and chronic obstructive pulmonary disease cohort, we confirmed the effects of PI Z heterozygote and compound heterozygote genotypes. We demonstrate the cumulative effects of multiple SERPINA1 variants on alpha-1 antitrypsin deficiency, lung function, and emphysema, thus significantly increasing the frequency of SERPINA1 variation associated with respiratory disease in at-risk smokers.

Omalizumab treatment in Samter's triad: case series and review of the literature.

OBJECTIVE: Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic. PATIENTS AND METHODS: We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. RESULTS: Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. CONCLUSIONS: The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.

Weight Status and Respiratory Health in Asthmatic Children.

In this study,we explored the effect of adiposity as measured by BMI on lung function in 72 asthmatic school children (5-12 years) using baseline data from the Mediterranean diet enriched with fatty fish intervention study. Bronchial function was assessed using spirometry and fractional exhaled nitric oxide (FeNO). BMI categories were classified as normal and overweight/obese based on International Obesity Task Force cut-offs. Weak correlations were observed between BMI and FVC (p = 0.013) and FEV1 (p = 0.026). Median FeNO was lower in the overweight/obese as compared to normal weight group (p = 0.027). Linear regression showed an increment in FEF25-75% in the overweight/obese group as compared to normal weight after controlling for confounders namely age, height, sex, regular physical activity, medication and KIDMED score (p = 0.043; ß = 11.65 units, 95% CI 0.36-22.94), although with no effect on FeNO. In conclusion, the findings of this study suggest that excess body weight could impact pulmonary dynamics in childhood asthma.

I Say IOS You Say AOS: Comparative Bias in Respiratory Impedance Measurements.

BACKGROUND: The forced oscillation technique (FOT) measures respiratory impedance during normal tidal breathing and requires minimal patient cooperation. OBJECTIVE: To compare IOS and AOS devices in patients with asthma and COPD. METHODS: We compared two different FOT devices, namely impulse oscillometry using a loudspeaker (IOS: Jaeger Masterscreen) and airwave oscillometry using a vibrating mesh (AOS: Thorasys Tremoflo) for pre- and post-bronchodilator measurements in 84 patients with asthma and COPD. RESULTS: The overall pattern of measurement bias was for higher resistance with IOS and higher reactance with AOS, this being the case in asthma and COPD separately. There were small but significantly higher values using IOS for resistance at 5 Hz (R5) and 20(19) Hz (R20(19)). In converse, values for reactance at 5 Hz (X5), reactance area (AX) and resonant frequency (Fres) were significantly higher using AOS but to a much larger extent. The difference in AX between devices was more pronounced in COPD than in asthma. Salbutamol reversibility as % change was greater in asthma than COPD patients with AX but not FEV1. CONCLUSION: Our study showed evidence of better agreement for resistance than reactance when comparing IOS and AOS, perhaps inferring that AOS may be more sensitive at measuring reactance in patients with airflow obstruction.

Circuit Training Improvements in Korean Women with Sarcopenia.

Sarcopenia is defined as an age-related decrease in muscle mass, strength, and function. We investigated the effect of circuit training on body composition, balance, muscle mass and strength, and pulmonary function in Korean women with sarcopenia. We randomly assigned 26 Korean women with sarcopenia (Mage = 74.9, SD = 4.5 years) to either an exercise group (EG) (n = 13) or a control group (CG) (n = 13). The EG performed 25-75 minutes of circuit exercise training (gradually increasing time periods) three times per week over 12 weeks, while the CG maintained their usual daily lifestyle during the intervention period. We measured body weight, body mass index, percent body fat, free fat mass, balance ability, peak torque in shoulder, knee, and lumbar joints normalized for bodyweight (BW), forced vital capacity, percentage of forced expiratory volume in one second, and forced expiratory flow 25-75% before and after the intervention. The EG showed improved body composition (i.e., body mass index, fat-free body mass, fat mass; all p < .032, η2 > 0.180), balance (i.e., right and left of static and dynamic balance and fast 10-m walk; all p < .050, η2 > 0.151), muscular function (i.e., 90°/s and 180°/s peak power per kilogram BW, 90°/s average power per kilogram BW, 180°/s total work, and 180°/s endurance ratio; all p < .045, η2 > 0.157), and pulmonary function (all p < .005, η2 > 0.292). On the other hand, the CG showed no significant changes. Circuit exercise training improves muscle mass and strength, body composition, balance, and pulmonary function in women with sarcopenia.