Fisiología respiratoria: fisiopatología de las enfermedades obstructivas / Pathophysiology of obstructive diseases

Las enfermedades obstructivas de la vía aérea pediátrica son muy frecuentes debido a los fenómenos mecánicos que están involucrados. En los niños más pequeños, la marcada resistencia de las vías aéreas pequeñas, determinada por la falta de tejido elástico y una caja torácica aún no bien desarrollada; tanto su estructura como la musculatura, facilitarán que cuadros infecciosos, mecánicos (cuerpo extraño) y compresivos, determinen que los flujos de aire se vean limitados y con ello la ventilación alveolar. La respuesta fisiológica con aumento del trabajo respiratorio es limitada y por lo tanto la fatiga muscular determinará hipoventilación con las consecuencias de hipoxemia e hipercapnia.

Obstructive diseases of the pediatric airway are very frequent due to the mechanical phenomena that are involved. The marked resistance of the small airways, such as the lack of elastic tissue and a thoracic cage that is not yet well developed, both in its structure and in the musculature, will make it easier for infectious, mechanical (foreign body), compressive and other conditions to determine that the flows of air are limited and with it the alveolar ventilation. The physiological response with increased work of breathing is limited and therefore muscle fatigue will determine hypoventilation, with the consequences of hypoxemia and hypercapnia.

Lung function and atherosclerosis: a cross-sectional study of multimorbidity in rural Uganda.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. METHODS: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. RESULTS: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (ß = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. CONCLUSIONS: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.

Impact of bronchial wall thickness on airflow obstruction in bronchiectasis.

The association between airflow obstruction and bronchial dilation has been researched in bronchiectasis. However, the impact of bronchial wall thickening on airflow obstruction has not been thoroughly investigated. This study assessed the underlying mechanism of airflow obstruction in bronchiectasis due to abnormal bronchial wall thickening using oscillometry. A total of 98 patients with bronchiectasis were retrospectively reviewed. At the time of diagnosis, spirometric and oscillometric parameters, high-resolution computed tomography scores, and clinical characteristics were collected. The bronchial diameter, bronchial wall thickness, and extent of emphysema were evaluated semi-quantitatively. Correlations between patient data and characteristics were analyzed. Thirty-three patients with airflow obstruction showed higher respiratory resistance, more negative respiratory reactance (Xrs) at 5 Hz (X5), and higher bronchial wall thickness score than those without airflow obstruction. The bronchial wall thickness score negatively affected forced expiration volume in 1 s /forced vital capacity and X5. Abnormal bronchial wall thickening might make Xrs more negative and progress airflow obstruction in bronchiectasis.

Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters.

BACKGROUND: Multiple breath washout (MBW) using sulfur hexafluoride (SF6) has the potential to reveal ventilation heterogeneity which is frequent in patients with obstructive lung disease and associated small airway dysfunction. However, reference data are scarce for this technique and mostly restricted to younger cohorts. We therefore set out to evaluate the influence of anthropometric parameters on SF6-MBW reference values in pulmonary healthy adults. METHODS: We evaluated cross-sectional data from 100 pulmonary healthy never-smokers and smokers (mean 51 (SD 20), range 20-88 years). Lung clearance index (LCI), acinar (Sacin) and conductive (Scond) ventilation heterogeneity were derived from triplicate SF6-MBW measurements. Global ventilation heterogeneity was calculated for the 2.5% (LCI2.5) and 5% (LCI5) stopping points. Upper limit of normal (ULN) was defined as the 95th percentile. RESULTS: Age was the only meaningful parameter influencing SF6-MBW parameters, explaining 47% (CI 33% to 59%) of the variance in LCI, 32% (CI 18% to 47%) in Sacin and 10% (CI 2% to 22%) in Scond. Mean LCI increases from 6.3 (ULN 7.4) to 8.8 (ULN 9.9) in subjects between 20 and 90 years. Smoking accounted for 2% (CI 0% to 8%) of the variability in LCI, 4% (CI 0% to 13%) in Sacin and 3% (CI 0% to 13%) in Scond. CONCLUSION: SF6-MBW outcome parameters showed an age-dependent increase from early adulthood to old age. The effect was most pronounced for global and acinar ventilation heterogeneity and smaller for conductive ventilation heterogeneity. No influence of height, weight and sex was seen. Reference values can now be provided for all important SF6-MBW outcome parameters over the whole age range. TRIAL REGISTRATION NUMBER: NCT04099225.

Severe Cardiopulmonary Disease in a Parturient With Noonan Syndrome.

Noonan syndrome is a relatively common genetic disorder and the second most common cause of congenital heart disease after trisomy 21. The spectrum of cardiac anomalies in Noonan syndrome typically involves pulmonary valve stenosis occasionally in conjunction with hypertrophic cardiomyopathy. Mitral valve involvement is a rare finding in Noonan syndrome and is most commonly associated with either mitral valve prolapse or abnormal valvular insertion causing left ventricular outflow tract obstruction. Patients with Noonan syndrome typically have preserved fertility and, given the success of cardiac surgery and medical management of heart failure in this population, are beginning to present more commonly as parturients in adulthood. Maternal physiologic changes during pregnancy introduce an added complexity to hemodynamic management and anesthetic considerations during labor and delivery. In this article, we present a case of a patient with Noonan syndrome with severe mitral stenosis, pulmonary valve insufficiency, and severe restrictive and obstructive pulmonary disease who presented preterm for delivery due to increased dyspnea at rest. Here we review the pathophysiology behind Noonan syndrome and peripartum management strategies in a patient with severe combined cardiac and pulmonary disease.

Outcome measures for airway clearance techniques in children with chronic obstructive lung diseases: a systematic review.

BACKGROUND: Airway clearance techniques (ACTs) are an important aspect of the treatment of children with chronic obstructive lung diseases. Unfortunately, a sound evidence base is lacking and airway clearance strategies are largely based on clinical expertise. One of the reasons for the limited evidence is the lack of appropriate outcome measures specifically related to the effectiveness of ACTs. This review discusses all outcome measures applied in previous research in the pediatric population to provide a baseline for future studies. DATA SOURCES: A systematic literature search was performed in PubMed, Web of Science and EMBASE databases. Search terms included chronic obstructive lung diseases and ACTs. STUDY SELECTION: Studies were independently selected by the investigators according to the eligibility criteria. After screening, 49 articles remained for further analysis. RESULTS AND CONCLUSIONS: Data are summarized according to the type of outcome measure. 48 (98%) studies performed pulmonary function tests, 19 (39%) assessed expectorated sputum, 10 (20%) parameters related to disease exacerbation, 8 (16%) oxygenation, 8 (16%) patient-reported outcomes, 5 (10%) exercise capacity and 5 (10%) applied imaging techniques. The synthesis of results showed a high discrepancy between studies due to differences in study design, population and the application of techniques. Since no 'gold standard' method could be identified, a combination of different outcome measures is recommended to gain a better understanding and to identify the potential effects of ACTs. An overview of important considerations has been provided to assist researchers in their choice of outcomes in future studies.

Pulmonary function and high-resolution computed tomography in outdoor rock drillers exposed to crystalline silica.

OBJECTIVES: Chronic obstructive pulmonary disease and silicosis are associated with exposure to crystalline silica. We determined the exposure to respirable crystalline silica and estimated exposure-response relationships between cumulative exposure and pulmonary function in outdoor rock drillers. METHODS: 136 rock drillers and 48 referents were recruited from three heavy construction companies. 98 air samples were collected by personal sampling for determination of respirable particulate matter and crystalline silica. Information about individual job tasks, type of drilling equipment and years of exposure in different job categories was obtained by interview. Cumulative exposure to crystalline silica was calculated for all workers. Pulmonary function was assessed by spirometry. A subgroup of 39 subjects with high cumulative exposure to crystalline silica underwent high-resolution computed tomography (HRCT). RESULTS: Cumulative exposure (mean (min-max)) to crystalline silica was 0.69 mgÙ years m-3 (0.01-5.89) in the exposed group. Mean time of exposure among rock drillers was 10.7 years (1-42). Compared with referents, the rock drillers had a lower forced expiratory volume in one second/forced vital capacity ratio (79.4 vs 81.4, p<0.05) and maximal mid-expiratory flow% (85.6 vs 93.9, p<0.05). Further, by stratifying the exposed workers into three equally large groups, a dose-response relationship was demonstrated in the highest exposed group, also in never smokers, at a mean cumulative exposure of 21.7 years at 0.08 mgÙ m-3/years. Silicosis was not detected in HRCT, but other patterns of fibrosis and emphysema were seen. CONCLUSIONS: Outdoor rock drillers exposed to crystalline silica had significantly lower pulmonary function than referents, and signs of airflow obstruction. Silicosis was not detected.

Lung function in adults and future burden of obstructive lung diseases in a long-term follow-up.

Spirometry is recommended in symptomatic smokers to identify obstructive lung diseases. However, it is unknown whether there are certain characteristics that can be used to identify the individual risk of developing obstructive lung diseases. The aim of this study was to examine the association between lung function in adults and burden of lung diseases throughout 27 years of follow-up. We performed a cohort study among individuals aged 30-49 years at baseline (1991). Spirometry measurements were divided into three groups: (1) FEV1/FVC < 70, (2) FEV1/FVC: 70-75, (3) FEV1/FVC > 75 (reference). Using negative binominal regression, the burden of lung diseases was measured by contacts to general practice, hospitalisations, redeemed respiratory medicine and socioeconomic parameters between 1991 and 2017. A total of 905 citizens were included; mean age of 40.3 years, 47.5% were males and 51.2% were smokers at baseline. The group with an FEV1/FVC: 70-75 received more respiratory medicine (IRR = 3.37 (95% CI: 2.69-4.23)), had lower income (IRR = 0.96 (95% CI: 0.93-0.98)), and had more contacts to general practice (IRR = 1.14 (95% CI: 1.07-1.21)) and hospitals for lung diseases (IRR = 2.39 (95% CI: 1.96-5.85)) compared to the reference group. We found an association between lung function and the future burden of lung diseases throughout 27 years of follow-up. In particular, adults with an FEV1/FVC: 70-75 need extra attention in the case finding.

Clinical and functional correlations of the difference between slow vital capacity and FVC / Correlação clínica e funcional da diferença entre capacidade vital lenta e CVF

ABSTRACT Objective: To evaluate the relationship that the difference between slow vital capacity (SVC) and FVC (ΔSVC-FVC) has with demographic, clinical, and pulmonary function data. Methods: This was an analytical cross-sectional study in which participants completed a respiratory health questionnaire, as well as undergoing spirometry and plethysmography. The sample was divided into two groups: ΔSVC-FVC ≥ 200 mL and ΔSVC-FVC < 200 mL. The intergroup correlations were analyzed, and binomial logistic regression analysis was performed. Results: The sample comprised 187 individuals. In the sample as a whole, the mean ΔSVC-FVC was 0.17 ± 0.14 L, and 61 individuals (32.62%) had a ΔSVC-FVC ≥ 200 mL. The use of an SVC maneuver reduced the prevalence of nonspecific lung disease and of normal spirometry results by revealing obstructive lung disease (OLD). In the final logistic regression model (adjusted for weight and body mass index > 30 kg/m2), OLD and findings of air trapping (high functional residual capacity and a low inspiratory capacity/TLC ratio) were predictors of a ΔSVC-FVC ≥ 200 mL. The chance of a bronchodilator response was found to be greater in the ΔSVC-FVC ≥ 200 mL group: for FEV1 (OR = 4.38; 95% CI: 1.45-13.26); and for FVC (OR = 3.83; 95% CI: 1.26-11.71). Conclusions: The use of an SVC maneuver appears to decrease the prevalence of nonspecific lung disease and of normal spirometry results. Individuals with a ΔSVC-FVC ≥ 200 mL, which is probably the result of OLD and air trapping, are apparently more likely to respond to bronchodilator administration.

RESUMO Objetivo: Avaliar a relação da diferença entre a capacidade vital lenta (CVL) e CVF (ΔCVL-CVF) com dados demográficos, clínicos e de função pulmonar. Métodos: Estudo analítico, transversal, no qual os participantes responderam a um questionário de saúde respiratória e foram submetidos a espirometria e pletismografia. A amostra foi dividida em dois grupos: ΔCVL-CVF ≥ 200 mL e ΔCVL-CVF < 200 mL. Foram realizadas análises de correlações entre os grupos e de regressão logística binominal. Resultados: Foram selecionados 187 indivíduos. Na amostra total, a média da ΔCVL-CVF foi de 0,17 ± 0,14 L. Na amostra, 61 indivíduos (32,62%) apresentaram ΔCVL-CVF ≥ 200 mL. O uso da manobra expiratória lenta reduziu a prevalência de distúrbio ventilatório inespecífico e resultados espirométricos normais, ao revelar distúrbio ventilatório obstrutivo (DVO). DVO e achados de aprisionamento aéreo (capacidade residual funcional elevada e capacidade inspiratória/CPT reduzida) foram preditores de ΔCVL-CVF ≥ 200 mL no modelo final da regressão logística (ajustada para peso e índice de massa corpórea > 30 kg/m2). Foi observada maior chance de resposta ao broncodilatador no grupo ΔCVL-CVF ≥ 200 mL: VEF1 (OR = 4,38; IC95%: 1,45-13,26) e CVF (OR = 3,83; IC95%: 1,26-11,71). Conclusões: O uso da manobra expiratória lenta diminuiu a prevalência de distúrbio ventilatório inespecífico e de resultados espirométricos normais, podendo a ΔCVL-CVF ≥ 200 mL ser resultado de DVO e aprisionamento aéreo, tendo maior chance de resposta ao broncodilatador.

The characteristics of the frequent exacerbators with chronic bronchitis phenotype and the asthma-chronic obstructive pulmonary disease overlap syndrome phenotype in chronic obstructive pulmonary disease patients: A meta-analysis and system review.

To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype.We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis.Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] -9.05, 95% confidence interval [CI] [-12.00, -6.10], P < .001, I = 66%), forced expiratory volume in 1 second (FEV1) (MD -407.18, 95% CI [-438.63, -375.72], P < .001, I = 33%), forced expiratory volume in 1 second percent predicted (MD -9.71, 95% CI [-12.79, -6.63], P < .001, I = 87%), FEV1/forced vital capacity (MD -5.4, 95% CI [-6.49, -4.30], P < .001, I = 0%), and body mass index (BMI) (MD -0.81, 95% CI [-1.18, -0.45], P < .001, I = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I = 86%) as compared to the ACO phenotype.Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx.This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.

Rational particle design to overcome pulmonary barriers for obstructive lung diseases therapy.

Pulmonary delivery of active drugs has been applied for the treatment of obstructive lung diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis, for several decades and has achieved progress in symptom management by bronchodilator inhalation. However, substantial progress in anti-inflammation, prevention of airway remodeling and disease progression is limited, since the majority of the formulation strategies focus only on particle deposition, which is insufficient for pulmonary delivery of the drugs. The lack of knowledge on lung absorption barriers in obstructive lung diseases and on pathogenesis impedes the development of functional formulations by rational design. In this review, we describe the physiological structure and biological functions of the barriers in various regions of the lung, review the pathogenesis and functional changes of barriers in obstructive lung diseases, and examine the interaction of these barriers with particles to influence drug delivery efficiency. Subsequently, we review rational particle design for overcoming lung barriers based on excipients selection, particle size and surface properties, release properties and targeting ability. Additionally, useful particle fabrication strategies and commonly used drug carriers for pulmonary delivery in obstructive lung diseases are proposed in this article.

Recurrent Inactive Hydatid Cyst of the Liver Causing Restrictive Pulmonary Physiology.

Hydatid and alveolar cysts are formed by the helminths Echinococcus granulosus and Echinococcus multilocularis, respectively, which are endemic to pastoral areas, and are more commonly found in South America, the Mediterranean, Russia, and China. Hydatid cysts can cause bacteremia, form abscesses, or cause mass effect by compressing surrounding organs. Strategies to prevent such complications include benzimidazoles, surgical resection, and Puncture, Aspiration, Injection and Re-aspiration (PAIR) procedure. A 71-year-old Egyptian man with remote history of Echinococcus infection one year status post PAIR procedure, presented with dyspnea on exertion. On exam, the patient had a palpable right upper quadrant mass. The patient had a known small hydatid liver cyst on prior ultrasound, however repeat imaging showed growth to 15×19×14cm, with right hemidiaphragm elevation, compressive atelectasis, and compression of the right atrium. He had no peripheral eosinophilia and negative echinococcal serology, consistent with remote infection. The patient underwent repeat PAIR procedure and 3L of serous fluid was drained from the cyst. Fluid analysis was negative for scolices, cysts or hooklets. His symptoms improved; however the cyst re-accumulated 1 month later. Total cystectomy was performed surgically by hepatic wedge resection, with permanent improvement in symptoms. This case is a rare example of Echinococcus infection causing significant respiratory morbidity requiring repeated invasive procedures and surgery, in the setting of inactive disease.

ENT involvement and orobuccal movements' disorders in Pandas patients: assessment and rehabilitations tools.

OBJECTIVE: PANDAS are known as the spectrum of autoimmune pathologies related to a previous or current infection by group A beta-hemolytic streptococcus (SBEGA), dealing with several neuropsychiatric manifestations that mainly affect pediatric age. The main features consist of behavioral disease or movement disease characterized by acute-onset, presenting especially through infant period or adolescence. Specific manifestations, occurring during the progression of the disease, are the presence of otorhinolaryngologic symptoms (ENT) and orofacial movement disorders associated with temporomandibular joint pain. PATIENTS AND METHODS: We enrolled 130 children (5-15 years) with a clinical diagnosis of PANDAS between 2012 and 2018. Participants were assessed using ENT specific parameters, PSG to examine respiratory disorders and conventional audiological evaluation. Descriptive and comparative statistical analyses were performed with a control group of 51 healthy patients. RESULTS: The prevalence of ENT symptoms associated was significantly detected in 88 patients of 130 in Group A (relative frequency (%) 67.6; p=0.041) and in 51 patients of 130 in the control Group B (relative frequency (%) 39.2; p=0.063). In relation to prevalence of SDB, 54 subjects have presented nocturnal respiratory obstructive symptoms from mild to severe (relative frequency (%) 61.3; p=0.033) vs. 20 patients of Group B (relative frequency (%) 39.2; p=0.055). The obstructive severity average type was correlated to the consensual adenotonsillar development (size 3-4), (relative frequency (%) 45.4; p=0.047). The audiological deficits found were mostly of transmissive type with OME correlated and linked to the presence of occasional episodes of AOM. The four PANDAS patients who presented orobuccal dystonia (relative frequency (%) 4.54; p=0.091) achieved an improvement of the algic symptoms through the exercises of self-rehabilitation. CONCLUSIONS: Findings from our study show that respiratory diseases, characterizing a group of patients with pandas, are the direct consequences of the malformed or hypertrophic condition and suggesting in these conditions surgical therapy as an approaching tool.

Predictors of accelerated FEV1 decline in adults with airflow limitation-Findings from the Health2006 cohort.

To investigate predictors of accelerated decline in forced expiratory volume in 1 s (FEV1) in individuals with preexisting airflow limitation (AL). Participants in the Health2006 baseline study aged ≥ 35 with FEV1/ forced vital capacity (FVC) < lower limit of normal (LLN) were invited for a 10-year follow-up. At both examinations, data were obtained on demographics, spirometry, fitness level, allergy, and exhaled nitric oxide. We used multiple regression modeling to predict the annual decline in FEV1, reported as regression coefficients ( R) and 95% confidence intervals (CIs). A total of 123 (43% of those invited) participated in the follow-up examination, where more had exercise-induced dyspnea but fewer had asthma symptoms. Being female ( R = -29.8 ml, CI: -39.7 to -19.8), diagnosed with asthma ( R = -13.7, CI: -20.4 to -7.0) or atopic dermatitis ( R = -29.0, CI: -39.7 to -18.4), and having current asthma symptoms or nightly respiratory symptoms ( R = -22.1, CI: -31.9 to -12.4 and R = -14.3, CI: -19.9 to -8.7, respectively) were significantly associated with a steeper decline in FEV1. Although to a smaller extent, a steeper decline was also predicted by age, baseline FEV1, waist/hip-ratio, and number of pack-years smoked. In individuals with preexisting AL, being female and having ever or current respiratory symptoms were associated with an accelerated annual decline in FEV1.

Respiratory muscles dysfunction and respiratory diseases.

This review presents an analysis of the literature on the topic of respiratory muscle (RM) dysfunction in various forms of respiratory pathology: chronic obstructive pulmonary disease (COPD), asthma, community-acquired pneumonia, idiopathic pulmonary fibrosis (IPF), sarcoidosis and interstitial lung diseases (ILD), associated with systemic connective tissue diseases (polymyositis, dermatomyositis and systemic lupus erythematosus - SLE). Various clinical and pathophysiological aspects of RM dysfunction and general patterns of its pathogenesis were examined. It was proved that the role of RM in the development of respiratory failure depends on the form and stage of the pulmonary pathology and the severity of systemic manifestations of these diseases: excessive proteolysis, oxidative stress, hypoxia, chronic systemic inflammation. These factors modify the morphofunctional status of RM, worsens their contractile function, which is contributed to the development of respiratory failure. In some cases, the primary weakness of RM precedes the clinical manifestation of pulmonary pathology, which is distinctive for some variants of myositis-associated ILD and SLE. Endogenous intoxication syndrome plays a significant role in the development of RM dysfunction during community-acquired pneumonia. It is noted that sarcoid pulmonary ventilation disorders associate with the RM weakness, but not with the degree of lung damage. In most cases, secondary RM dysfunction predominates that contributes to respiratory failure progression, which is especially noticeable in case of COPD, asthma and IPF.

Pulmonary function abnormalities are common in patients with multiple myeloma and are independently associated with worse outcome.

Pre-existing pulmonary disease may affect treatment choices, toxicity, and survival of patients with multiple myeloma (MM). However, data on the prognostic value of pulmonary function tests (PFTs) in myeloma patients' outcome, at the time of initial assessment of newly diagnosed patients, are scarce. Here, we prospectively performed PFTs in 121 newly diagnosed MM patients, before initiation of treatment, and we evaluated possible associations of lung function with their outcomes. Fifty-four patients (44.63%) had either obstructive or restrictive pulmonary function defects, even among those not reporting a history of lung disease. The survival was significantly worse in those with obstructive pulmonary defect (median OS 32.8 months) vs. those with restrictive (median OS 52.5 months) or normal lung function (median not reached, 3-year survival 76%) (p = 0.013), independently of other myeloma-related factors. Forced vital capacity (FVC) (lt) (p = 0.012), forced expiratory volume in 1 s (FEV1) (lt) (p = 0.018), peak expiratory flow (PEF) (lt/min) (p = 0.008), carbon monoxide diffusion capacity (DLCO) (p = 0.012), and expiratory/inspiratory pressures (Pe) (kPa) (p = 0.032)/(Pi) (kPa) (p = 0.023) were significantly associated with OS. Myeloma-related factors associated with survival included ISS stage (p = 0.008), hypercalcemia (p = 0.064), and high-risk cytogenetics (p = 0.004). In the multivariate analysis, only the presence of high-risk cytogenetics and presence of either or both PEF and DLCO < 65% of predicted were independent prognostic factors. We conclude that PEF and DLCO could be useful in the initial assessment of newly diagnosed MM patients as significant predictors of survival. Further research is needed to evaluate if respiratory screening should be included in the routine initial evaluation of myeloma patients, despite the presence or absence of respiratory symptoms or abnormal clinical respiratory examination.

Single-breath washout and association with structural lung disease in children with cystic fibrosis.

BACKGROUND: In children with cystic fibrosis (CF) lung clearance index (LCI) from multiple-breath washout (MBW) correlates with structural lung disease. As a shorter test, single-breath washout (SBW) represents an attractive alternative to assess the ventilation distribution, however, data for the correlation with lung imaging are lacking. METHODS: We assessed correlations between phase III slope (SIII) of double-tracer gas SBW, nitrogen MBW indices (LCI and moment ratios for overall ventilation distribution, Scond, and Sacin for conductive and mainly acinar ventilation, respectively) and structural lung disease assessed by chest computed tomography (CT) in children with CF. RESULTS: In a prospective cross-sectional study data from MBW, SBW, and chest CT were obtained in 32 children with CF with a median (range) age of 8.2 (5.2-16.3) years. Bronchiectasis was present in 24 (75%) children and air trapping was present in 29 (91%). Median (IQR) SIII of SBW was -138.4 (150.6) mg/mol. We found no association between SIII with either the MBW outcomes or CT scores (n = 23, association with bronchiectasis extent r = 0.10, P = 0.64). LCI and Scond were associated with bronchiectasis extent (n = 23, r = 0.57, P = 0.004; r = 0.60, P = 0.003, respectively). CONCLUSIONS: Acinar ventilation inhomogeneity measured by SBW was not associated with structural lung disease on CT. Double-tracer SBW added no benefit to indices measured by MBW.

GLI 2012 equations define few spirometric anomalies in the general population: the PneumoLaus study.

BACKGROUND: Reduced lung function predicts increased mortality, but its prevalence may vary depending on definition considered, use of bronchodilation and applied reference values. We aimed to assess lung function abnormalities in Lausanne, Switzerland, and their association with clinical history. METHODS: In a general population sample, spirometry was performed and bronchodilation applied if the ratio forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) or the FVC was below the lower limit of normal (LLN) according to Global Lung Function Initiative 2012 references. Results for FEV1/FVC according to the LLN were compared to the 0.7 fixed ratio. Respiratory risk factors, symptoms and self-reported respiratory diagnoses were recorded through a questionnaire. RESULTS: Out of the 3342 included subjects, 3.8% had chronic obstruction and 2.5% reversible obstruction when using the LLN; possible lung restriction alone was present in 1.8%, and associated with chronic obstruction in 0.4%. Ever smokers had a higher prevalence of abnormal spirometry, chronic obstruction and reversible obstruction; there was no difference with regard to possible restriction. Overall, chronic airway obstruction was found in 8.9% of current smokers, 4.6% of former smokers and 1.5% of never smokers. Only one third of participants with chronic obstruction were aware of a respiratory disease. CONCLUSION: Prevalence of abnormal lung function in the population of Lausanne is low. This may be due to a low rate of ever-smokers, the application of a full bronchodilation dose, but also to inherent characteristics of this population.

Harmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study.

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.