¿Se puede utilizar la determinación del pico flujo de tos para valorar la capacidad tusígena en enfermedades respiratorias obstructivas graves? / Can cough peak flow be used to assess cough capacity in severe obstructive respiratory diseases?

Introducción: La valoración de la capacidad tusígena se realiza con la medición del flujo espiratorio máximo durante la tos (peak-flow tos [PFT]). Sin embargo, esta valoración podría alterarse por enfermedades con obstrucción espiratoria de la vía aérea. El objetivo fue valorar la medición de la capacidad tusígena mediante PFT en pacientes con enfermedad pulmonar obstructiva crónica (EPOC), así como las correlaciones con la función pulmonar, muscular respiratoria y orofaríngea. Métodos: Se seleccionaron los pacientes con EPOC y con enfermedad neuromuscular, así como los sujetos sanos a los que se había realizado una medición de la fuerza de los músculos respiratorios de forma asistencial. De esta población, se analizaron los valores de la función respiratoria, así como la fuerza muscular orofaríngea. En un subgrupo de pacientes con EPOC se realizó el estudio de deglución por videofluoroscopia. Resultados: Se incluyeron 307 sujetos (59,3% EPOC, 38,4% enfermedades neuromusculares y 2,3% sanos). En el grupo EPOC, el PFT se encontraba disminuido de forma estadísticamente significativa comparado tanto con el grupo de los sanos como con los enfermos neuromusculares. El 70% de los EPOC tenían una disminución patológica del PFT. Solamente, existía una correlación directa entre el PFT con el grado de obstrucción bronquial y la fuerza de los músculos espiratorios. No se encontró alteración de la función de los músculos inspiratorios ni orofaríngeos. Conclusiones: La utilización del PFT en los pacientes con EPOC no refleja la capacidad tusígena ya que se ve influenciada por el grado de obstrucción bronquial. Por tanto, se deberían valorar nuevas pruebas diagnósticas para la medición de la capacidad tusígena, fundamentalmente, en los pacientes que coexistan enfermedades neuromusculares y patología obstructiva bronquial grave.(AU)

Introduction: Cough capacity is assessed by measuring cough peak flow (CPF). However, this assessment could be altered by obstructive airway diseases. The aim was to assess measurement of cough capacity by CPF in patients with chronic obstructive pulmonary disease (COPD), as well as correlations with pulmonary, respiratory muscle, and oropharyngeal function. Methods: Patients with COPD, and with neuromuscular disease, were selected as well as healthy subjects who had undergone respiratory muscle strength measurement in a healthcare setting. From this population, respiratory function values and lung and oropharyngeal muscle function were analysed. A subgroup of COPD patients underwent a videofluoroscopic swallow study. Results: Three hundred and seven subjects were included (59.3% COPD, 38.4% neuromuscular diseases, and 2.3% healthy). CPF was found to be statistically significantly decreased in the COPD group compared to both the healthy and neuromuscular disease groups. Of the COPD patients, 70% had a pathological decrease in CPF. There was only a direct correlation between CPF with the degree of bronchial obstruction and expiratory muscle strength. No alteration of inspiratory or oropharyngeal muscle function was found. Conclusions: The use of CPF in COPD patients does not reflect cough capacity as it is influenced by the degree of bronchial obstruction. Therefore, new diagnostic tests to measure cough capacity should be considered, especially in patients with coexisting neuromuscular diseases and severe bronchial obstructive disease.(AU)

Sex modifies the risk of HIV-associated obstructive lung disease in Ugandans postpneumonia.

OBJECTIVES: Spirometric abnormalities are frequent, and obstructive lung disease (OLD) is a common comorbidity among people with HIV (PWH). HIV increases the risk of many comorbidities to a greater degree in women than in men. Few studies have evaluated whether sex modifies the HIV-associated risk of OLD. DESIGN AND METHODS: To evaluate the associations between sex and HIV with abnormal lung function, women and men with and without HIV underwent spirometric testing after completing therapy for pneumonia, including tuberculosis (TB), in Kampala, Uganda. OLD was defined as a postbronchodilator forced expiratory volume in the first second to forced vital capacity (FEV 1 /FVC) ratio less than 0.70. Associations between sex, HIV, and lung function were evaluated using multivariable regression models including sex-by-HIV interaction terms after adjusting for age, BMI, smoking status, and TB status. RESULTS: Among 348 participants, 147 (42%) were women and 135 (39%) were HIV-positive. Sixteen (11%) women and 23 men (11%) had OLD. The HIV-sex interaction was significant for obstructive lung disease ( P  = 0.04). In the adjusted stratified analysis, women with HIV had 3.44 (95% CI 1.11-12.0; P  = 0.04) increased odds of having OLD compared with men with HIV. Women without HIV did not have increased odds of having OLD compared with men without HIV. CONCLUSION: HIV appears to increase the risk of OLD to a greater degree in women than in men in an urban Ugandan setting. The mechanistic explanation for this interaction by sex remains unclear and warrants further study.

Causes of hypercapnic respiratory failure and associated in-hospital mortality.

BACKGROUND AND OBJECTIVE: Hypercapnic respiratory failure (HRF) can occur due to severe respiratory disease but also because of multiple coexistent causes. There are few data on the prevalence of antecedent causes for HRF and the effect of these causes on prognosis, especially where study inclusion has not been biased with respect to primary diagnosis, interventions received or clinical outcome. We sought to determine the prevalence of pre-specified conditions among patients with HRF and to determine the effect of these causes on in-hospital mortality. METHODS: Cross-sectional study of patients with HRF from 2013 to 2017. Inclusion criteria were PaCO2  >45 mm Hg and pH ≤7.45. Causes of interest were identified using diagnosis codes from hospital records. We used directed acyclic graphs to inform logistic regression models for the outcome of in-hospital death. RESULTS: We identified 873 persons with HRF in the study period. Mean (SD) age was 69 years and 50.4% were males. Acidosis (pH <7.35) was present in 488 (55%) cases. Most (83%) had one or more of the following: obstructive lung disease, lower respiratory tract infection, congestive cardiac failure, sleep disordered breathing, neuromuscular disease, opioid or benzodiazepine use. In-hospital mortality was 12.8%. Obstructive lung disease and cardiac failure were associated with a lower risk of death, whereas respiratory tract infection and neuromuscular disease were associated with increased risk of death. CONCLUSION: HRF is associated with a range of potentially causative conditions, which significantly impact hospital survival. Systematic evaluation of patients with HRF may increase detection of treatable comorbidities.

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.

Afectación respiratoria en paciente con acrodisostosis: una asociación infrecuente de una enfermedad rara / Respiratory impairment in a patient with acrodysostosis: A rare association of an uncommon pathology

La acrodisostosis es una displasia esquelética rara, de herencia autosómica dominante, que se caracteriza por la presencia de disostosis facial y periférica, talla baja y diferentes grados de obesidad. La acrodisostosis de tipo 1, secundaria a la mutación heterocigota en el gen PRKAR1A (17q24.2), se caracteriza por la asociación de resistencia hormonal múltiple con anomalías esqueléticas. Su incidencia está infradiagnosticada debido a que comparte rasgos clínicos y de laboratorio con otras entidades como el seudohipoparatiroidismo. Presentamos el caso de una niña de 8 años, con acrodisostosis tipo 1, confirmada mediante estudio genético. Además del fenotipo característico descrito, la talla baja y la resistencia hormonal, la paciente presentó una afectación progresiva de la función pulmonar: un patrón pulmonar obstructivo no reversible. En la literatura revisada, no se han encontrado otros casos que describan esta asociación entre acrodisostosis y afectación respiratoria.

Acrodysostosis is a rare skeletal displasia, of autosomal dominant inheritance, characterized by the presence of facial and peripheral dysostosis, short stature and obesity. Type 1 acrodysostosis is secondary to a mutation in the PRKAR1A (17q24.2) gene, which results in multi hormonal resistance and skeletal anomalities. This syndrome is under-diagnosed as it shares analytical and clinical characteristics with other entities, such as pseudohypoparathyroidism. We report the case of an eight-year-old girl with genetically confirmed type 1 acrodysostosis. In addition to the characteristic phenotype described, the short stature and the hormonal resistance, the patient suffered a progressive lung function deterioration: an irreversible pulmonary obstructive pattern. We have not found in previous literature cases reporting an association between acrodysostosis and lung function impairement.

Group 3 Pulmonary Hypertension: A Review of Diagnostics and Clinical Trials.

Group 3 pulmonary hypertension (PH) is a known sequelae of chronic lung disease. Diagnosis and classification can be challenging in the background of chronic lung disease and often requires expert interpretation of numerous diagnostic studies to ascertain the true nature of the PH. Stabilization of the underlying lung disease and adjunctive therapies such as oxygen remain the mainstays of therapy, as there are no Food and Drug Administration-approved therapies for group 3 PH. Referral to PH centers for individualized management and clinical trial enrollment is paramount.

The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I.

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed.

Expression of ACE2 in airways: Implication for COVID-19 risk and disease management in patients with chronic inflammatory respiratory diseases.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a rising international cause of morbidity and mortality. Angiotensin-converting enzyme 2 (ACE2) is identified as a key cell entry receptor for SARS-CoV-2 and suggested to be a limiting factor for viral entry at the initial infection stage. Recent studies have demonstrated that ACE2 expression is highly enriched in nasal epithelial cells and type II alveolar epithelial cells, highlighting the importance of respiratory tract as the primary target site of SARS-CoV-2. The expression of ACE2 in airway epithelial cells is tightly regulated by inflammatory milieu and environmental and internal stimuli. Very recently, ACE2 has been reported to have different expression levels in airways under distinct chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and allergic asthma, which may associate with the COVID-19 risk and affect the management of primary airway diseases. In this review, we focus on the cutting-edge progress in distribution, expression, and regulation of ACE2 in respiratory system in physiological and pathological conditions, and their implication for the development of COVID-19. We also discuss the management of airway diseases, including asthma, COPD, allergic rhinitis, and rhinosinusitis in the era of COVID-19.

Pulmonary Comorbidities Are Associated with Increased Major Complication Rates Following Indwelling Interscalene Nerve Catheters for Shoulder Arthroplasty.

Pulmonary comorbidities and ASA physical status class III and IV can significantly increase the rate of major complications after ISC placement. Patients with an underlying pulmonary comorbidity or lung disease (chronic obstructive pulmonary disease, asthma, or obstructive sleep apnea) have a 2.2-fold increased risk of having any complication and a 2.4-fold increased risk of having a major pulmonary complication compared to those without pulmonary comorbidities. Patients with pulmonary comorbidities may benefit from alternative pain management strategies to avoid complications in the early postoperative period.

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.

Prevalence and correlates of obstructive lung disease among people who inject drugs, San Diego, California.

BACKGROUND: Pulmonary tissue damage leading to obstructive lung disease (OLD) could result from intravenous administration of insoluble particles found in illicit drugs. This study described the prevalence and identified correlates of OLD among people who inject drugs (PWID). METHODS: In 2012-2016, a community-based cohort of PWID who had injected within the past month were enrolled in a study to assess HIV, hepatitis C virus (HCV) andMycobacterium tuberculosis (Mtb) infections and their related risk factors. Data were obtained through face-to-face interviews, serological testing and spirometry. Baseline data were used for a cross-sectional analysis of the prevalence and correlates of OLD, defined as FEV1/FVC < 0.7. Univariate and multivariable logistic regression were used to identify factors associated with OLD. RESULTS: Among 516 participants who had complete spirometry and interview results, the mean age was 43.3 years, 73.6 % were male, 9.5 % were Black, 91.1 % smoked cigarettes and 18.2 % had OLD. Few (9.6 %) PWID with OLD reported a previous diagnosis of COPD although many (44.7 %) reported related symptoms. Black race (AOR = 2.66, 95 %CI: 1.37, 5.17), pack-years smoked (AOR = 1.06/5 years, 95 %CI: 1.01, 1.12), and duration of injection drug use (AOR = 1.13, 95 %CI: 1.01, 1.27) were independently associated with OLD after controlling for age. CONCLUSIONS: The prevalence of OLD was high in this cohort and associated with Black race and cigarette smoking-known risk factors. In addition, OLD prevalence increased with greater duration of injection drug use, suggesting a link between cumulative exposure to injected insoluble particles and OLD. Further examination of these adulterants and lung pathology are needed.

Prevalence of, and risk factors for underweight or excess weight in patients with chronic obstructive emphysema from a multiethnic region of Xinjiang, China.

BACKGROUND: The purpose of this study is to assess the basic nutritional status (body metabolic index, BMI) and its risk factors in the patients suffering from chronic obstructive emphysema. METHODS: We described their demographic characteristics and comorbidity distribution of 2812 obstructive emphysema participants. Comparative analyzes were conducted on BMI with different demographic characteristics and comorbidities status, and comprehensive analysis on risk factors of excess weight and underweight in patients with different characters. RESULTS: The prevalence of underweight and excess weight was 17.57% and 31.54% respectively. There were differences in the distribution of three types of body mass index among patients with different demographic characteristics and different comorbidities. The study found that age of 50 ~ 64 (odds ratio, OR: 2.99), tuberculosis (OR: 2.41), and low TG (OR: 2.32) were the risk factors about underweight. Low HDL-C (OR: 4.15), nonalcoholic fatter liver (NAFLD) (OR: 3.96), and age of 50 ~ 64 (OR: 2.72) were closely related to the excess weight of participants. CONCLUSIONS: This study highlighted the prevalence of underweight and excess weight in patients among emphysema. Comorbidities were important risk factors of underweight or excess weight among chronic emphysema patients. These findings were important for the prevention and treatment of chronic obstructive emphysema in the future.

Endothelial Activation, Innate Immune Activation, and Inflammation Are Associated With Postbronchodilator Airflow Limitation and Obstruction Among Adolescents Living With HIV.

BACKGROUND: Chronic inflammation, innate immune activation, T-cell imbalance and endothelial activation have been linked with lung diseases. We sought to determine whether markers of these pathophysiologic pathways were associated with spirometry and chest computed tomography (CT) abnormalities among adolescents living with HIV (ALWH). SETTING: Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. METHODS: We performed a cross-sectional study of ALWH (10-19 years old). Participants underwent chest CT, spirometry, and venipuncture for serum biomarkers. We also collected demographic, anthropometric, T-cell subset, antiretroviral therapy, and exposure data. We compared characteristics and biomarkers by airflow obstruction [postbronchodilator FEV1/FVC z-score (zFEV1/FVC) < -1.64]. We used multivariable linear regression to determine associations of log10-transformed biomarkers and chest CT abnormalities with lower postbronchodilator zFEV1/FVC (airflow limitation). We performed exploratory principal components analysis on biomarkers, and determined associations of factors with postbronchodilator zFEV1/FVC and chest CT abnormalities. RESULTS: Of 47 participants with acceptable quality spirometry, 21 (45%) were female, median age was 13 years and 96% had perinatally-acquired HIV. Median CD4 was 672 cells/µL. Overall, 28% had airflow obstruction and 78% had a chest CT abnormality; airflow obstruction was associated with mosaic attenuation (P = 0.001). Higher endothelial activation (sVCAM-1, sICAM-1), inflammation and innate immune activation (serum amyloid-A, sTREM-1, sCD163), and T-cell imbalance (lower CD4/CD8) markers were associated with airflow limitation. Factors comprising endothelial and innate immune activation were associated with airflow limitation. CONCLUSIONS: Endothelial activation, innate immune activation, T-cell imbalance, and chronic inflammation are associated with airflow limitation and obstruction, providing insights into chronic lung disease pathophysiology among ALWH.

Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression.

BACKGROUND: Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO2) on development of pancreatic ductal adenocarcinoma (PDAC) and drug resistance. STUDY DESIGN: Two PDAC cell lines were exposed to normocapnic (5% CO2) and hypercapnic (continuous/intermittent 10% CO2) conditions, physiologically similar to patients with active ORD. Cells were assessed for proliferation rate, colony formation, and chemo-/radiotherapeutic efficacy. In a retrospective clinical study design, patients with PDAC who had undergone pancreatic resection between 2002 and 2014 were reviewed. Active smokers were excluded to remove possible smoking-related protumorigenic influence. Clinical data, pathologic findings, and survival end points were recorded. Kaplan-Meier and Cox regression analyses were performed. RESULTS: Exposure to hypercapnia resulted in increased colony formation and proliferation rates in vitro in both cell lines (MIA-PaCa-2: 111% increase and Panc-1: 114% increase; p < 0.05). Hypercapnia exposure induced a 2.5-fold increase in oxaliplatin resistance (p < 0.05) in both cell lines and increased resistance to ionizing radiation in MIA-PaCa-2 cells (p < 0.05). Five hundred and seventy-eight patients were included (52% were male, median age was 68.7 years [interquartile range 60.6 to 76.8 years]). Cox regression analysis, assessing TNM staging, age, sex, and ORD status, identified ORD as an independent risk factor for both overall survival (hazard ratio 1.64; 95% CI, 1.2 to 2.3; p < 0.05) and disease-free survival (hazard ratio 1.68; 95% CI, 1.06 to 2.67). CONCLUSIONS: PDAC cells exposed to hypercapnic environments, which is common in patients with ORD, showed tumor proliferation, radioresistance, and chemoresistance. Patients with a history of ORD had a worse overall prognosis, suggesting that hypercapnic conditions play a role in the development and progression of PDAC and stressing the need for patient-tailored care.

Ultrasound-guided lumbar selective nerve root block plus T12 paravertebral and sacral plexus block for hip and knee arthroplasty: Three case reports.

RATIONALE: For hip or knee arthroplasty, it is essential to develop a satisfied peripheral nerve block method that will benefit elderly patients or patients who are contraindicated to neuraxial anesthesia. PATIENTS CONCERNS: Patient in Case 1 suffered from the right intertrochanteric fracture, combined with chronic obstructive pulmonary disease; Patient in Case 2 suffered from hip osteoarthritis; combined with ankylosing spondylitis; Patient in Case 3 suffered from rheumatoid arthritis, combined with ischemic encephalopathy. DIAGNOSIS: Case 1: Right intertrochanteric fracture, chronic obstructive pulmonary disease. Case 2: hip osteoarthritis. Case 3: rheumatoid arthritis. INTERVENTIONS: Ultrasound-guided lumbar selective nerve root block (SNRB) plus T12 paravertebral and sacral plexus block were performed in 2 patients who received hip arthroplasty and 1 patient who received knee arthroplasty. OUTCOMES: All patients successfully received surgeries with this peripheral nerve block method and no postoperative complication was reported. LESSONS: Ultrasound-guided lumbar SNRB plus T12 paravertebral and sacral plexus block not only satisfied the analgesia requirement of surgery, but also reduced the consumption of local anesthetic.

External Validation and Recalculation of the CODEX Index in COPD Patients. A 3CIAplus Cohort Study.

The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25-75% 426-1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (≤3 months), medium- (≤1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (<1 year) than the original CODEX, and similarly in the long-term. In conclusion, CODEX and mCODEX index are good predictors of mortality in patients with COPD, regardless of disease severity or duration of follow-up.

Club Cell Secretory Protein Deficiency Leads to Altered Lung Function.

RATIONALE: CC16 (club cell secretory protein-16), a member of the secretoglobin family, is one of the most abundant proteins in normal airway secretions and has been described as a serum biomarker for obstructive lung diseases. OBJECTIVES: To determine whether low CC16 is a marker for airway pathology or is implicated in the pathophysiology of progressive airway damage in these conditions. METHODS: Using human data from the birth cohort of the Tucson Children's Respiratory Study, we examined the relation of circulating CC16 levels with pulmonary function and responses to bronchial methacholine challenge from childhood up to age 32 years. In wild-type and CC16-/- mice, we set out to comprehensively examine pulmonary physiology, inflammation, and remodeling in the naive airway. MEASUREMENTS AND MAIN RESULTS: We observed that Tucson Children's Respiratory Study participants in the lowest tertile of serum CC16 had significant deficits in their lung function and enhanced airway hyperresponsiveness to methacholine challenge from 11 years throughout young adult life. Similarly, CC16-/- mice had significant deficits in lung function and enhanced airway hyperresponsiveness to methacholine as compared with wild-type mice, which were independent of inflammation and mucin production. As compared with wild-type mice, CC16-/- mice had significantly elevated gene expression of procollagen type I, procollagen type III, and α-smooth muscle actin, areas of pronounced collagen deposition and significantly enhanced smooth muscle thickness. CONCLUSIONS: Our findings support clinical observations by providing evidence that lack of CC16 in the lung results in dramatically altered pulmonary function and structural alterations consistent with enhanced remodeling.

Rate control and clinical outcomes in patients with atrial fibrillation and obstructive lung disease.

BACKGROUND: Rate-control medications are considered first-line treatment for patients with atrial fibrillation (AF). However, obstructive lung disease (OLD), a condition prevalent in those with AF, often makes it difficult to use those medications because of the lack of studies on new-onset AF in patients with OLD. OBJECTIVE: The purpose of this study was to investigate clinical outcomes after administration of each class of rate-control medication in patients with concomitant AF and OLD (AF-OLD). METHODS: This study used the entire database provided by the National Health Insurance Service from 2002 to 2015. Risk of all-cause mortality was compared between use of calcium channel blocker (CCB) and use of other drug classes in AF-OLD patients using Cox regression analyses after propensity score matching. RESULTS: Among the 13,111 patients, the number of AF-OLD patients treated with a CCB, cardioselective ß-blocker (BB), nonselective BB, and digoxin was 2482, 2379, 2255, and 5995, respectively. The risk of mortality was lower with use of selective BB (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75-0.94; P = .002) and nonselective BB (HR 0.85; 95% CI 0.77-0.95; P = .003) compared to use of CCBs. Digoxin use was related with worse survival, with marginal statistical significance (HR 1.09; 95% CI 1.00-1.18; P = .053). CONCLUSION: Among patients with AF-OLD, rate-control treatment using selective and nonselective BB was associated with a significant reduction in mortality compared with CCB use. Further prospective randomized trials are required to confirm these findings.

Influenza vaccine for chronic obstructive pulmonary disease (COPD).

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies, with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in people with COPD, but there is also the potential for influenza vaccination to cause adverse effects, or not to be cost effective. OBJECTIVES: To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective. SEARCH METHODS: We searched the Cochrane Airways Trials Register, two clinical trials registries, and reference lists of articles. A number of drug companies we contacted also provided references. The latest search was carried out in December 2017. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. All entries were double-checked. We contacted study authors and drug companies for missing information. We used standard methods expected by Cochrane. MAIN RESULTS: We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) -0.37, 95% confidence interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient.There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.