Phase 2, Double-Blind, Placebo-controlled Trial of a c-Jun N-Terminal Kinase Inhibitor in Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. Objectives: We sought to assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. Methods: In a Phase 2, randomized (1:1:1), double-blind, placebo-controlled study (ClinicalTrials.gov ID: NCT03142191), patients received CC-90001 (200 or 400 mg) or placebo once daily for 24 weeks. Background antifibrotic treatment (pirfenidone) was allowed. The primary endpoint was change in the percentage of predicted FVC (ppFVC) from baseline to Week 24; secondary endpoints included safety. Measurements and Main Results: In total, 112 patients received at least one dose of study drug. The study was terminated early because of a strategic decision made by the sponsor. Ninety-one patients (81%) completed the study. The least-squares mean changes from baseline in ppFVC at Week 24 were -3.1% (placebo), -2.1% (200 mg), and -1.0% (400 mg); the differences compared with placebo were 1.1% (200 mg; 95% confidence interval: -2.1, 4.3; P = 0.50) and 2.2% (400 mg; 95% confidence interval: -1.1, 5.4; P = 0.19). Adverse event frequency was similar in patients in the combined CC-90001 arms versus placebo. The most common adverse events were nausea, diarrhea, and vomiting, which were more frequent in patients in CC-90001 arms versus placebo. Fewer patients in the CC-90001 arms than in the placebo arm experienced cough and dyspnea. Conclusions: Treatment with CC-90001 over 24 weeks led to numerical improvements in ppFVC in patients with idiopathic pulmonary fibrosis compared with placebo. CC-90001 was generally well tolerated, which was consistent with previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT03142191).

Fat mass to fat-free mass ratio and its associations with clinical characteristics in asthma.

BACKGROUND: Fat mass to fat-free mass ratio (FM/FFM) assesses the combined effect of the balance between fat mass and fat-free mass. AIMS: to evaluate the associations beetween FM/FFM and clinical outcomes in asthma and to compare clinical characteristics between individuals with higher and lower FM/FFM. METHODS: 128 participants with asthma underwent anthropometric, spirometry and bioelectrical impedance assessments. Physical activity in daily life (PADL) was assessed by the Actigraph for 7 days. Daily dose of inhaled medication, steps of pharmacological treatment, Asthma Control Questionnaire, Asthma Quality of Life Questionnaire and Hospital Anxiety and Depression Scale were also assessed. Participants were classified into two groups according to the 50th percentile of reference values for FM/FFM. RESULTS: Individuals with higher FM/FFM (n=75) used higher daily doses of inhaled corticosteroids, had worse lung function and fewer steps/day when compared to those with lower FM/FFM (n=53) (P≤0.021). Associations were found between absolute values of FM/FFM with lung function (FEV1 and FVC [liters]): R2=0.207 and 0.364;P<0.0001), and between the categories of lower or higher FM/FFM with steps of medication treatment (Cramer's V=0.218;P=0.016) and level of PADL (Cramer's V=0.236;P=0.009). The highest FM/FFM was a determining factor of physical inactivity (OR: 3.21;95%CI:1.17-8.78) and highest steps of pharmacological treatment (OR: 8.89;95%CI:1.23-64.08). CONCLUSION: Higher FM/FFM is significantly associated with worse clinical characteristics in individuals with asthma, such as higher doses of inhaled corticosteroids, worse lung function and fewer steps/day. Moreover, higher FM/FFM is a determining factor of physical inactivity and the highest steps of pharmacological treatment for asthma.

FEV1/FEV6 y FEV6 una alternativa para FEV1/FVC y FVC en la detección de obstrucción de vías respiratorias / FEV1/FEV6 and FEV6 an alternative for FEV1/FVC and FVC in the detection of airway obstruction

INTRODUCCIÓN: el objetivo de este estudio fue verificar si los puntos de corte fijos y el límite inferior de lo normal (LLN) para el volumen espiratorio forzado en un segundo (FEV1) y el volumen espiratorio forzado en 6 segundos (FEV6) FEV1/FEV6 y el FEV6 son una medida alternativa para el FEV1 y la capacidad vital forzada (FVC), FEV1/FVC y la FVC en la detección de la enfermedad pulmonar obstructiva crónica (EPOC), en una muestra de pacientes del oriente boliviano. MÉTODOS: se analizaron un total de 92 pruebas espirométricas, 66 varones y 26 mujeres con riesgo de EPOC. La población del estudio incluyó a residentes de la ciudad de Santa Cruz de la Sierra-Bolivia (ciudad cosmopolita) de 35 a 90 años de edad. RESULTADOS: la sensibilidad y la especificidad fueron del 97,0% y el 96,9%, respectivamente, cuando se compararon los valores de corte fijos de FEV1/FEV6 de 0,73 con los de FEV1/FVC < 0,7 como regla estándar, según las recomendaciones del global obstructive lung diseases (GOLD) para detectar la obstrucción de las vías respiratorias. La sensibilidad y la especificidad fueron de 93,4% y 81,2%, respectivamente, cuando el LLN de FEV1/FVC y FEV1/FEV6 fueron utilizados. CONCLUSIONES: en conclusión, el FEV6 es un sustituto válido de la CVF para detectar la obstrucción de las vías respiratorias, ya sea utilizando puntos de corte fijos o el LLN. Se necesitan más estudios para verificar estos resultados en una población más grande y para establecer los valores predictivos espirométricos locales.

INTRODUCTION: the aim of this study was to verify if fixed cut-off points and lower limit of normal (LLN) for forced expiratory volume in one second (FEV1)/FEV6 and FEV6 as an alternative for FEV1/forced vital capacity (FVC) and FVC are valid for the detection of obstructive lung disease in a sample of Bolivian subjects. METHODS: a total of 92 spirometric consecutive tests from subjects, 66 males and 26 females at risk for COPD were analyzed. The study population included residents of city Santa Cruz de la Sierra, (Bolivia) aged from 35 to 90 yrs., from various ethnical origins (cosmopolitan city). RESULTS: sensibility and specificity were 97.0% and 96.9%, respectively when fixed cut-off values of FEV1/FEV6 of 0.73 was compared to FEV1/FVC<0.7 as standard, according to GOLD recommendations to detect airway obstruction. Sensibility and specificity were 100% and 89.5%, respectively when LLN of FEV1/FVC and FEV1/FEV6 were used. CONCLUSIONS: in conclusion, FEV6 is a valid surrogate for FVC to detect airway obstruction, either using fixed cut-off points or LLN. Further study is needed to verify these results in a larger population and to establish local spirometric predicted values

The Relationship of IL-8 and IL-10 Myokines and Performance in Male Marathon Runners Presenting Exercise-Induced Bronchoconstriction.

At present, it is unclear which exercise-induced factors, such as myokines, could diminish the negative impact of the reduction in pulmonary function imposed by the exercise in question. In this study, we aim to evaluate the prevalence of exercise-induced bronchoconstriction (EIB) and also to investigate the effect of myokines in the performance of marathon runners presenting EIB or not. Thirty-eight male recreational marathon runners (age 38.8 [33-44], height 175.7 [172.0-180.3]; weight 74.7 [69.3-81.6]) participated in this study, and through spirometry tests, a prevalence of 23.6% of EIB was found, which is in agreement with the literature. The volunteers who tested positive to EIB (EIB+) presented lower maximum aerobic capacity compared to those who tested negative (EIB-) (EIB+ 44.02 [39.56-47.02] and EIB- 47.62 [44.11-51.18] p = 0.03). The comparison of plasma levels of IL-1ß (EIB+ p = 0.296, EIB- p = 0.176, EIB+ vs. EIB- baseline p = 0.190 immediately after p = 0.106), IL-4 (undetectable), IL-6 (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.301 immediately after p = 0.614), IL-8 (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.110 immediately after p = 0.453), IL-10 (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.424 immediately after p = 0.876) and TNF-α (EIB+ p = 0.003, EIB- p ≤ 0.001, EIB+ vs. EIB- baseline p = 0.141 immediately after p = 0.898) were similar in both groups 24 h before and immediately after the marathon. However, negative correlations were found between the marathon finishing time and the levels of IL-8 (r = -0.81, p = 0.022), and IL-10 (r = -0.97, p ≤ 0.001) immediately after completing the marathon. In conclusion, for the first time, it is shown that the myokines IL-8 and IL-10 are related to improvement of the performance of marathon runners presenting EIB.

COPD: Gaps in the GOLD Recommendations and Related Imperative Research Needs.

The GOLD 2020 updates added more lucidity on the treatment of COPD. However, few diagnostic dilemmas still exist. Research is needed on the use of the CAT score in assessing symptoms for the diagnosis of COPD. Further work-up is needed on diagnostic instability of spirometry, and diagnostic role of the lower limit of normal (LLN) criteria, slow vital capacity (FEV1/VC), forced inspiratory vital capacity (FEV1/FIVC), and rapid FEV1 decline. Incorporating parameters of lung hyperinflation and exercise capacity in the COPD diagnostic criteria might add value in its diagnosis and management. GOLD's approach towards routine CT imaging needs to be reviewed. Establishing a "pre-COPD" stage can be helpful in the early diagnosis and intervention to reduce the rapid lung function decline among at-risk individuals. The use of mMRC score as a surrogate to assess the overall severity of COPD related symptoms should be reviewed. The therapeutic guidance role of sputum eosinophils should be studied in patients with intermediate and low blood eosinophil counts.

Longitudinal Analysis of Pulmonary Function in Survivors of Congenital Diaphragmatic Hernia.

OBJECTIVE: To analyze longitudinal trends of pulmonary function testing in patients with congenital diaphragmatic hernia (CDH) followed in our multidisciplinary clinic. STUDY DESIGN: This was a retrospective cohort study of CDH patients born between 1991 and 2013. A linear mixed effects model was fitted to estimate the trends of percent predicted forced expiratory volume in 1 second (FEV1pp), percent predicted forced vital capacity (FVCpp), and FEV1/FVC over time. RESULTS: Of 268 patients with CDH who survived to discharge, 119 had at least 1 pulmonary function test study. The FEV1pp (P < .001), FVCpp (P = .017), and FEV1/FVC (P = .001) decreased with age. Compared with defect size A/B, those with defect size C/D had lower FEV1pp by an average of 11.5% (95% CI, 2.9%-20.1%; P = .010). A history of oxygen use at initial hospital discharge also correlated with decreased FEV1pp by an average of 8.0% (95% CI, 1.2%-15.0%; P = .023). CONCLUSIONS: In a select cohort of CDH survivors, average pulmonary function declines with age relative to expected population normative values. Those with severe CDH represent a population at risk for worsening pulmonary function test measurements who may benefit from recognition and monitoring for complications.

Comparison of Pulmonary Function Decline in Steroid-Treated and Steroid-Naïve Patients with Duchenne Muscular Dystrophy.

OBJECTIVE: To describe and compare the lung function decline in patients with Duchenne muscular dystrophy on glucocorticoid therapy in contrast with glucocorticoid-naïve patients, and to define the deciles of pulmonary decline in glucocorticoid-treated patients. STUDY DESIGN: This retrospective study examined lung function of patients with Duchenne muscular dystrophy over 6 years of age followed between 2001 and 2015 at 2 centers-glucocorticoid-treated patients in Cincinnati, Ohio, and glucocorticoid-naïve patients in Paris, France. Forced vital capacity (FVC, FVC%), forced expiratory volume in 1 second, maximal inspiratory pressure, maximal expiratory pressure, and peak expiratory flow data were analyzed. Only FVC data were available for the French cohort. RESULTS: There were 170 glucocorticoid-treated patients (92%), 5 patients (2.7%) with past glucocorticoid use, and 50 French glucocorticoid-naïve patients. The peak absolute FVC was higher and was achieved at earlier ages in glucocorticoid-treated compared with glucocorticoid-naïve patients (peak FVC, 2.4 ± 0.6 L vs 1.9 ± 0.7 L; P < .0001; ages 13.5 ± 3.0 years vs 14.3 ± 2.8 years; P = .03). The peak FVC% was also higher and was achieved at earlier ages in glucocorticoid-treated patients (peak FVC%, 105.1 ± 25.1% vs 56 ± 20.9%; P < .0001; ages 11.9 ± 2.9 years vs 13.6 ± 3.2 years; P = .002). Rates of decline for both groups varied with age. Maximal rates of decline were 5.0 ± 0.26% per year (12-20 years) for glucocorticoid-treated and 5.1 ± 0.39% per year for glucocorticoid-naïve patients (11-20 years; P = .2). Deciles of FVC% decline in glucocorticoid-treated patients show that patients experience accelerated decline at variable ages. CONCLUSIONS: These data describe nonlinear rates of decline of pulmonary function in patients with Duchenne muscular dystrophy, with improved function in glucocorticoid-treated patients. FVC% deciles may be a useful tool for clinical and research use.

Declining Lung Function and Cardiovascular Risk: The ARIC Study.

BACKGROUND: Pulmonary dysfunction predicts incident cardiovascular disease (CVD). OBJECTIVES: The purpose of this study was to evaluate whether longitudinal decline in lung function is associated with incident heart failure (HF), coronary heart disease (CHD), and stroke. METHODS: Among 10,351 participants in the ARIC (Atherosclerosis Risk In Communities) study free of CVD, rapid lung function decline was defined as the greatest quartile (n = 2,585) of decline in either forced expiratory volume in 1 s (FEV1) (>1.9% decline/year) or forced vital capacity (FVC) (>2.1% decline/year) over 2.9 ± 0.2 years. The relationship between rapid decline in FEV1 or FVC and subsequent incident HF, CHD, stroke, or a composite of these was assessed using multivariable Cox regression adjusting for the baseline spirometry value, demographics, height, body mass index, heart rate, diabetes, hypertension, low-density lipoprotein, use of lipid-lowering medication, N-terminal fragment of prohormone for B-type natriuretic peptide, and smoking. RESULTS: The mean age was 54 ± 6 years, 56% were women, and 81% were white. At 17 ± 6 years of follow-up, HF occurred in 14%, CHD 11%, stroke 6%, and the composite in 24%. Rapid decline in FEV1 and in FVC were both associated with a heightened risk of incident HF (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.33; p = 0.010; and HR: 1.27; 95% CI: 1.12 to 1.44; p < 0.001; respectively), with rapid decline in FEV1 most prognostic in the first year of follow-up (HR: 4.22; 95% CI: 1.34 to 13.26; p = 0.01). Rapid decline in FEV1 was also associated with incident stroke (HR: 1.25; 95% CI: 1.04 to 1.50; p = 0.015). CONCLUSIONS: A rapid decline in lung function, assessed by serial spirometry, is associated with a higher incidence of subsequent CVD, particularly incident HF.

Respiratory and other health risks among poultry-farm workers and evaluation of management practices in poultry farms

The current study was conducted on eight poultry farms in Lahore and Sheikhupura to monitor environmental conditions, determine workers’ health status and assess the implementation of standard management practices. Environmental monitoring, a health questionnaire survey and a respiratory function test were carried out. Seventy-one respondents were selected for the health assessment survey and lung function test. The results showed that the evaluated air-quality parameters, except for temperature and humidity, were well below the permissible occupational limits. Maximum temperature recorded was 32.75 ºC, while the highest humidity level was 85.5%. Farms were shown to be compliant with standard guidelines and management practices. The workers’ health survey indicated lower prevalence of work-related symptoms as compared to previous studies. However, most workers were not subjected to overall physical hazards, 21.1% of workers suffered from heat-induced dermatosis, and 38% suffered from heat exhaustion. Eye problems (watery, redness and itchiness) were experienced by 16.9% to 31%. Reported respiratory symptoms included wheezing during colds (18.3%), wheezing other than during colds (1.4%), chest tightness (16.9%), shortness of breath along with chest tightness (9.9%), regular breathing difficulties (14.1%), and coughing (15.5%). Observed lung function pattern, as measured by FEV1/FVC ratio, was 87 ± 17.7, with 65% workers having ‘restrictive’ disorder and 21% normal lung function pattern, while 21% presented ‘obstructive’ lung function. The study concludes an overall better health and safety management in the selected poultry farms.

Respiratory and other health risks among poultry-farm workers and evaluation of management practices in poultry farms

The current study was conducted on eight poultry farms in Lahore and Sheikhupura to monitor environmental conditions, determine workers health status and assess the implementation of standard management practices. Environmental monitoring, a health questionnaire survey and a respiratory function test were carried out. Seventy-one respondents were selected for the health assessment survey and lung function test. The results showed that the evaluated air-quality parameters, except for temperature and humidity, were well below the permissible occupational limits. Maximum temperature recorded was 32.75 ºC, while the highest humidity level was 85.5%. Farms were shown to be compliant with standard guidelines and management practices. The workers health survey indicated lower prevalence of work-related symptoms as compared to previous studies. However, most workers were not subjected to overall physical hazards, 21.1% of workers suffered from heat-induced dermatosis, and 38% suffered from heat exhaustion. Eye problems (watery, redness and itchiness) were experienced by 16.9% to 31%. Reported respiratory symptoms included wheezing during colds (18.3%), wheezing other than during colds (1.4%), chest tightness (16.9%), shortness of breath along with chest tightness (9.9%), regular breathing difficulties (14.1%), and coughing (15.5%). Observed lung function pattern, as measured by FEV1/FVC ratio, was 87 ± 17.7, with 65% workers having ‘restrictive disorder and 21% normal lung function pattern, while 21% presented ‘obstructive lung function. The study concludes an overall better health and safety management in the selected poultry farms.(AU)

Spirometric instability - another hurdle in achieving real-world COPD diagnostic criteria?

Globally, mortality, morbidity and the economic burden of chronic obstructive pulmonary disease (COPD) are on the rise. In addition, its diagnosis continues to pose challenges to the physicians, which is compounded further by its new feature "spirometric instability." Based on the findings from the two recent observational studies, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended repeat spirometry for the individuals with a fixed ratio between 0.6 and 0.8. In this perspective, we discuss the uncertainties and consequences of this critical update in the 2018 GOLD report.

Metabolomic profiling of lung function in Costa-Rican children with asthma.

BACKGROUND: The development of novel therapeutics and treatment regimens for the management of asthma is hindered by an incomplete understanding of its heterogeneous nature and pathophysiology. Metabolomics can provide an integrated and global profile of a biological system in a dysregulated state, making it a valuable tool to identify biomarkers along the disease development pathway and to understand the biological mechanisms driving that pathway. METHODS: Liquid chromatography-mass spectrometry metabolomic profiling was conducted on plasma samples provided at recruitment for 380 children with asthma from the 'Genetic Epidemiology of Asthma in Costa Rica Cohort'. Metabolites associated with three clinical characteristics of asthma severity (i) airway hyper-responsiveness (AHR) (ii) percent-predicted forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), and (iii) FEV1/FVC post-bronchodilator were identified and their discriminatory ability assessed. Metabolite set enrichment analyses was applied to explore the biology underlying these relationships. RESULTS: AHR was associated (p<0.05) with 91 of 574 metabolites (15.9%), FEV1/FVC pre-bronchodilator with 102(17.8%), and FEV1/FVC post-bronchodilator with 155 (27.0%). The findings suggest that these characteristics capture some common and some distinct phenotypic aspects of lung function; glycerophospholipid, linoleic acid and pyrimidine metabolism were common to all three characteristics. The corresponding metabolomic profiles showed moderate but robust discriminatory ability. CONCLUSIONS: The results confirm the existence of an asthma severity metabolome. However, differences in the metabolomic profiles of the three lung function characteristics studied, suggest that refinement of both phenotype classification and metabolite selection should be a priority as the field of asthma metabolomics progresses.

Spirometry reference values in the Brazilian population

The aim of the present study was to provide new spirometry reference equations in a sample of the Brazilian population for the following parameters: forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, peak of expiratory flow (PEF), forced expiratory flow at 50% (FEF50%), 75% average vital capacity (FEF25-75%), and average forced expiratory flow time (FEFT). This was a prospective study using results from chest radiographs, electrocardiograms, and questionnaires to investigate the participants' respiratory symptoms, sedentarism, and comorbidities (Charlson comorbidity index). From December 2010 to July 2014, individuals were randomly selected from various locations in the state of Rio de Janeiro. All individuals were examined by a single technician in the morning at the laboratory, and performed the spirometry with the same spirometer. Spirometry values were tabulated for the creation of three equation models: linear regression, logarithmic regression, and logarithms through a method that incorporates the lambda, median, and coefficient of variation (LMS method). Initially, 7003 individuals from both genders were contacted, and 454 were recruited. The data from the new equations were compared with one Brazilian and eight international equations, resulting in a high correlation (r>0.9). The values derived from the LMS method and linear regression were very similar (P>0.5), and both could be used to acquire the reference values for Brazilian spirometry. Data derived from the equations of this study were different from the current Brazilian equation, which could be justified by the different method used.

Relationship Between Patient-Reported Outcomes and Clinical Outcomes in Patients With Morquio A Syndrome

Abstract This cross-sectional analysis assessed the correlation between patient-reported outcomes (PROs) and clinical outcomes in 24 German patients with Morquio A. Clinical outcomes included 6-minute walk test (6MWT), 3-minute stair climb (3MSC) test, and joint range of motion as measures for endurance/mobility, forced vital capacity (FVC) and maximum voluntary ventilation (MVV) as measures for respiratory function, and height as an important manifestation. The PROs included the EuroQoL (EQ) 5D-5L (EQ5D-5L), to measure health-related QoL (HRQoL), and patients' rating of their ability to walk, climb, or breathe. In adults, endurance and pulmonary function measures and height showed strong and statistically significant correlation with the patients' EQ5D-5L (6MWT: R = .884, 3MSC test: R = .852, FVC: R = .815, MVV: R = .825, height: R = .842). The adult patients' rating of their ability to walk and climb also correlated strongly with 6MWT (R = .839) and 3MSC test (R = .700) results. Improvements in these clinical outcomes may be robust surrogate parameters of a better EQ5D-5L/HRQoL in patients with Morquio A.

PIKO-6® vs. forced spirometry in asthmatic children.

BACKGROUND: The PIKO-6® is an electronic device that measures forced expiratory volume at seconds 1 (FEV1) and 6 (FEV6) of a forced vital capacity (FVC) maneuver. This device could aid in diagnosing obstructive respiratory diseases. OBJECTIVES: To determine the concordance of FEV1, FEV6, and the FEV1/FEV6 quotient achieved with PIKO-6® versus spirometric values from asthmatic patients, and compare results with measures from healthy children. METHODS: A cross-sectional study with asthmatic and healthy 6-to-14-year-old children, all of whom performed a forced spirometry as well as a PIKO-6® test. RESULTS: The study included 82 subjects (58 asthmatics, 24 healthy children). Except for the functional parameters, the basal characteristics of the two groups were similar. The concordance correlation coefficient (CCC) for FEV1 was 0.938 (P < 0.001), with 95% limits of agreement of -0.591 to 0.512 L, and an average of differences of -0.040 L. For FEV6, CCC was 0.927 (P < 0.001), and the 95% limits of agreement were -0.751 to 0.598 L with an average of differences of -0.077 L. The concordance analysis and the FEV1 and FEV6 associations were better in children with controlled asthma and healthy subjects, as well as in the post-bronchodilator results. CONCLUSIONS: The concordance between PIKO-6® and spirometry was lower in patients with partially controlled or uncontrolled asthma compared to controlled or healthy children. The broad limits of agreement show that the FEV1, FEV6, and FEV1/FEV6 obtained with the PIKO-6® are not interchangeable with spirometry results. Longitudinal evaluations of asthma patients are necessary to assess the utility of PIKO-6®.

Pulmonary outcome in former preterm, very low birth weight children with bronchopulmonary dysplasia: a case-control follow-up at school age.

OBJECTIVE: To assess and compare long-term pulmonary outcomes in former preterm-born, very low birth weight (VLBW) children with and without bronchopulmonary dysplasia (BPD) born in the surfactant era. STUDY DESIGN: Pulmonary function tests (ie, spirometry, body plethysmography, and gas transfer testing) were performed in children with a history of VLBW and BPD (n = 28) and compared with a matched preterm-born VLBW control group (n = 28). Medical history was evaluated by questionnaire. RESULTS: At time of follow-up (mean age, 9.5 years), respiratory symptoms (36% vs 8%) and receipt of asthma medication (21% vs 0%) were significantly more frequent in the preterm-born children with previous BPD than in those with no history of BPD. The children with a history of BPD had significantly lower values for forced expiratory volume in 1 second (z-score -1.27 vs -0.4; P = .008), forced vital capacity (z-score -1.39 vs -0.71 z-score; P = .022), and forced expiratory flow rate at 50% of forced vital capacity (z-score -2.21 vs -1.04; P = .048) compared with the preterm control group. CONCLUSION: Preterm-born children with a history of BPD are significantly more likely to have lung function abnormalities, such as airway obstruction and respiratory symptoms, at school age compared with preterm-born children without BPD.

Prematurity, atopy, and childhood asthma in Puerto Ricans.

BACKGROUND: Puerto Rican children share a disproportionate burden of prematurity and asthma in the United States. Little is known about prematurity and childhood asthma in Puerto Rican subjects. OBJECTIVE: We sought to examine whether prematurity is associated with asthma in Puerto Rican children. METHODS: We performed a case-control study of 678 children aged 6 to 14 years with (n = 351) and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was defined by parental report for our primary analysis. In a secondary analysis, we only included children whose parents reported prematurity that required admission to the neonatal intensive care unit. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for analysis. All multivariate models were adjusted for age, sex, household income, atopy (≥1 positive IgE level to common allergens), maternal history of asthma, and early-life exposure to environmental tobacco smoke. RESULTS: In a multivariate analysis there was a significant interaction between prematurity and atopy on asthma (P = .006). In an analysis stratified by atopy, prematurity was associated with a nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio, 4.7; 95% CI, 1.5-14.3; P = .007). In contrast, there was no significant association between prematurity and asthma in nonatopic children. Similar results were obtained in our analysis of prematurity requiring admission to the neonatal intensive care unit and asthma. CONCLUSIONS: Our results suggest that atopy modifies the estimated effect of prematurity on asthma in Puerto Rican children. Prematurity might explain, in part, the high prevalence of atopic asthma in this ethnic group.

Evaluation of lung function and deposition of aerosolized bronchodilators carried by heliox associated with positive expiratory pressure in stable asthmatics: a randomized clinical trial.

While administration of medical aerosols with heliox and positive airway pressure are both used clinically to improve aerosol delivery, few studies have differentiated their separate roles in treatment of asthmatics. The aim of this randomized, double blinded study is to differentiate the effect of heliox and oxygen with and without positive expiratory pressure (PEP), on delivery of radiotagged inhaled bronchodilators on pulmonary function and deposition in asthmatics. 32 patients between 18 and 65 years of age diagnosed with stable moderate to severe asthma were randomly assigned into four groups: (1) Heliox + PEP (n = 6), (2) Oxygen + PEP (n = 6), (3) Heliox (n = 11) and (4) Oxygen without PEP (n = 9). Each group received 1 mg of fenoterol and 2 mg of ipratropium bromide combined with 25 mCi (955 Mbq) of Technetium-99m and 0.9% saline to a total dose volume of 3 mL placed in a Venticis II nebulizer attached to a closed, valved mask with PEP of 0 or 10 cm H2O. Both gas type and PEP level were blinded to the investigators. Images were acquired with a single-head scintillation camera with the longitudinal and transverse division of the right lung as regions of interest (ROIs). While all groups responded to bronchodilators, only group 1 showed increase in FEV1%predicted and IC compared to the other groups (p < 0.04). When evaluating the ROI in the vertical gradient we observed higher deposition in the middle and lower third in groups 1 (p = 0.02) and 2 (p = 0.01) compared to group 3. In the horizontal gradient, a higher deposition in the central region in groups 1 (p = 0.03) and 2 (p = 0.02) compared to group 3 and intermediate region of group 2 compared to group 3. We conclude that aerosol deposition was higher in groups with PEP independent of gas used, while bronchodilator response with Heliox + PEP improved FEV1 % and IC compared to administration with Oxygen, Oxygen with PEP and Heliox alone. Trial registration NCT01268462.

Effectiveness of pulmonary rehabilitation in exercise capacity and quality of life in chronic obstructive pulmonary disease patients with and without global fat-free mass depletion.

OBJECTIVE: To investigate the effectiveness of pulmonary rehabilitation (PR) in exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD) with and without global fat-free mass (FFM) depletion. DESIGN: Retrospective case-control. SETTING: Outpatient clinic, university center. PARTICIPANTS: COPD patients (N=102) that completed PR were initially evaluated. INTERVENTION: PR including whole-body and weight training for 12 weeks, 3 times per week. MAIN OUTCOME MEASURES: St. George Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and FFM evaluation applied before and after PR. RESULTS: Patients were stratified according to their FFM status measured by bioelectric impedance. They were considered depleted if the FFM index was ≤ 15 kg/m(2) in women and ≤ 16 kg/m(2) in men. From the initial sample, all depleted patients (n=31) composed the FFM depleted group. It was composed predominantly by women (68%) with a mean age ± SD of 64.4 ± 7.3 years and a forced expiratory volume in 1 second of 33.6%=-13.2% predicted. Paired for sex and age, 31 nondepleted patients were selected from the initial sample to compose the nondepleted group. Improvement in the 6MWD was similar in these 2 groups after PR. Both groups improved SGRQ scores, although the observed power was small and did not allow adequate comparison between depleted and nondepleted patients. There was no difference between groups in weight change, whereas FFM tended to be greater in depleted patients. This increase had no correlation with the 6MWD or the SGRQ. CONCLUSIONS: Benefits of PR to exercise capacity were similar comparing FFM depleted and nondepleted COPD patients. Although FFM change tended to be greater in depleted patients, this increase had no definite relation with clinical outcomes.