Acute exacerbation of idiopathic pulmonary fibrosis (IPF) occurs in roughly 10% of patients annually, and is a leading cause of morbidity and mortality in this disease. While currently defined as idiopathic acute worsenings, acute exacerbations of IPF may in fact have a variety of causes, in particular infection and aspiration. Central to the pathobiology of clinically meaningful events is a diffuse injury to the IPF lung manifest histopathologically as diffuse alveolar damage, and biologically as accelerated alveolar epithelial cell injury or repair. Based on these recent observations, we propose a new paradigm for acute exacerbation of IPF that removes the idiopathic requirement and focuses on the pathophysiological mechanism involved.
Idiopathic Pulmonary Fibrosis; Acute exacerbation; Interstitial Lung Disease; Definition; Diagnosis; Management
Habitual smoking of marijuana is associated with multiple respiratory symptoms such as cough, sputum production, and wheezing .These symptoms are not significantly different from those exhibited by tobacco smokers. Furthermore, endobronchial biopsies of habitual smokers of marijuana and /or tobacco have shown that both marijuana and cigarette smoking cause significant bronchial mucosal histopathology and that these effects are additive. Although marijuana smokers have minimal changes in pulmonary function studies as compared to tobacco smokers, they may develop bullous disease and spontaneous pneumothoraces. The relationship between marijuana smoking and lung cancer remains unclear due to design limitations of the studies published so far. These findings should warn individuals that marijuana smoking may result in serious short-term and long-term respiratory complications, and habitual marijuana use should be viewed with caution. The medical literature so far does not support routine evaluation by pulmonary function tests or imaging studies; until more definitive data is available, we do not recommend the regular use of these tests in the evaluation of habitual marijuana smokers.
Habitual smoking; Marijuana; THC; Respiratory care
It is estimated that more than two billion people have latent M. tuberculosis infection, and this population serves as an important reservoir for future tuberculosis cases. Prevalence estimates are limited by difficulties in diagnosing the infection, including the lack of an ideal test, and an incomplete understanding of latency. Current tests include the tuberculin skin test and two interferon-γ release assays: QuantiFERON Gold In-Tube and T-SPOT.TB. This update focuses on recent publications regarding the ability of these tests to predict tuberculosis disease, their reproducibility over serial tests, and discordance between tests. We also discuss recent advances in the treatment of latent M. tuberculosis infection, including the three-month regimen of once-weekly rifapentine plus isoniazid, and prolonged isoniazid therapy for HIV-infected persons living in high-tuberculosis-incidence settings. We provide an update on the tolerability of the three-month regimen.
Latent tuberculosis infection; Tuberculin skin test; Interferon gamma release assay; QuantiFERON-TB gold in tube assay; T-SPOT. TB assay
COPD is thought to develop as a result of chronic exposure to cigarette smoke, occupational or other environmental hazards and it comprises both airways and parenchyma. Acute infections or chronic colonization of airways with bacteria may also contribute to development and/or progression of COPD lung disease. Airway epithelium is the primary target for the inhaled environmental factors and pathogens. The repetitive injury as a result of chronic exposure to environmental factors may result in persistent activation of pathways involved in airway epithelial repair, such as epithelial to mesenchymal transition, altered migration and proliferation of progenitor cells, and abnormal redifferentiation leading to airway remodeling. Development of model systems which mimics chronic airways disease as observed in COPD is required to understand the molecular mechanisms underlying the abnormal airway epithelial repair that are specific to COPD and to also develop novel therapies focused on airway epithelial repair.
barrier function; mucociliary clearance; innate immunity; asthma; EMT; airway progenitor cells; cigarette smoke; respiratory infection; EGFR; mucus metaplasia; mucus hyperplasia
This literature review updates the reader on the new studies regarding steroid therapy over the last year in stable COPD and in exacerbations. In stable COPD, we critique the 2011 update and 2013 revision of the GOLD guidelines, discuss why combining inhaled corticosteroids (ICS) with long-acting beta-agonists (LABA) (ICS/LABA) is preferable over LABA alone and review the literature for intraclass differences, finding that the evidence does not clearly support superiority of any particular ICS/LABA. We also address other comparisons against ICS/LABA, including triple therapy. We briefly review which type of inhaler should be chosen. For exacerbations, we report the REDUCE trial findings favouring a 5-day course of systemic steroids, and other trials addressing which steroid and route to use, including in an intensive care setting. Lastly, the future lies in new anti-inflammatories and re-phenotyping the heterogeneous amalgamation of COPD. A Spanish guideline recommends distinguishing steroid-responsive eosinophilic exacerbators from other phenotypes.
Corticosteroids; COPD; Drug therapy; Fluticasone; Budesonide; Beclometasone; Ciclesonide; Mometasone; Salmeterol; Formoterol; Vilanterol; Tiotropium; Glycopyrronium; Inhaler; MDI; DPI; Phenotype; Heterogeneity; Withdrawal; Exacerbation
The Childhood Asthma Management Program (CAMP) has been in continuous existence for almost two decades, which makes it the largest randomized, placebo-controlled clinical trial with extended follow-up for children with mild to moderate asthma. As such, its cumulative data from baseline, active treatment, and post-treatment have proved to be an invaluable resource for not only assessing the efficacy and safety of long-term inhaled corticosteroid therapy in childhood, but for discovery of many other aspects of childhood asthma, including genetics and biomarkers.
Asthma; childhood; spirometry; airway hyperresponsiveness; inhaled corticosteroids; bronchodilators; bronchodilator response; allergy; pharmacogenomics; bone mineral density; vitamin D; linear growth; cataracts; hypothalamic–pituitary–adrenal axis; remission; progression; exacerbation; oral corticosteroids; nedocromil; forced expiratory volume in one second (FEV1); forced vital capacity (FVC); symptoms; health care utilization; phenotype; genetic polymorphism; eosinophils
Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly-/dermatomyositis (PM/DM), Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease (MCTD) can all be associated with the development of ILD. Non-specific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP) may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs.
connective tissue disease; interstitial lung disease; autoimmune disease; pulmonary fibrosis; rheumatoid arthritis; dermatomyositis; polymyositis; Sjogren’s syndrome; progressive systemic sclerosis; systemic lupus erythematosus; mixed connective tissue disease; undifferentiated connective tissue disease; lung-dominant connective tissue disease
Antibody-mediated rejection after lung transplantation remains enigmatic. However, emerging evidence over the past several years suggests that humoral immunity plays an important role in allograft rejection. Indeed, the development of donor-specific antibodies after transplantation has been identified as an independent risk factor for acute cellular rejection and bronchiolitis obliterans syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in severe allograft dysfunction have been reported, and these demonstrate that antibodies can directly injure the allograft. However, the incidence and toll of antibody-mediated rejection are unknown because there is no widely accepted definition and some cases may be unrecognized. Clearly, humoral immunity has become an important area for research and clinical investigation.
antibody-mediated rejection; lung transplantation; hyperacute rejection; bronchiolitis obliterans syndrome; antibodies to human leukocyte antigens; donor-specific antibodies; complement component 4d deposition
For patients experiencing acute respiratory failure due to a severe exacerbation of chronic obstructive pulmonary disease (COPD), noninvasive positive pressure ventilation has been shown to significantly reduce mortality and hospital length of stay compared to respiratory support with invasive mechanical ventilation. Despite continued improvements in the administration of noninvasive ventilation (NIV), refractory hypercapnia and hypercapnic acidosis continue to prevent its successful use in many patients. Recent advances in extracorporeal gas exchange technology have led to the development of systems designed to be safer and simpler by focusing on the clinical benefits of partial extracorporeal carbon dioxide removal (ECCO2R), as opposed to full cardiopulmonary support. While the use of ECCO2R has been studied in the treatment of acute respiratory distress syndrome (ARDS), its use for acute hypercapnic respiratory during COPD exacerbations has not been evaluated until recently. This review will focus on literature published over the last year on the use of ECCO2R for removing extra CO2 in patients experiencing an acute exacerbation of COPD.
Extracorporeal carbon dioxide removal; Chronic obstructive pulmonary disease; Acute exacerbation; Acute hypercapnic respiratory failure; Hypercapnia; Hypercarbia; Extracorporeal gas exchange; Noninvasive ventilation; Mechanical ventilation; Hemolung; Novalung; Extracorporeal membrane oxygenation; Active mixing; Respiratory dialysis
Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients.
Severe asthma; Difficult-to-treat asthma; Asthma control; Exacerbation