Patients with chronic obstructive pulmonary disease (COPD) are prone to acute respiratory exacerbations, which can develop suddenly or subacutely over the course of several days. Exacerbations have a ...detrimental effect on patients’ health status and increase the burden on the healthcare system. Initial treatment is unsuccessful in 24-27% of patients, who have a relapse or a second exacerbation within 30 days of the initial event. No obvious benefit has been seen in recent clinical trials of anti-tumour necrosis factor therapy, anti-leukotriene therapy, intensive chest physiotherapy, or early inpatient pulmonary rehabilitation for treatment of exacerbations. By contrast, clinical trials of prevention rather than acute treatment have shown promising results. Long acting β agonist (LABA) or long acting anti-muscarinic (LAMA) bronchodilators and inhaled corticosteroid-LABA combinations prevent exacerbations in patients at risk, with relative risk reductions averaging 14-27% for each of these drugs relative to placebo. Triple therapy with inhaled corticosteroid-LABA plus LAMA may provide additional benefit, although study results to date are heterogeneous and more studies are needed. Pneumonia is an important complication of treatment with inhaled corticosteroid-LABA products, and the risk of pneumonia seems to be doubled in patients with COPD who use fluticasone. The addition of azithromycin to usual COPD therapy prevents exacerbations, although it may prolong the Q-T interval and increase the risk of death from cardiovascular disease in patients prone to arrhythmia. New potential drugs—including mitogen activated protein kinase inhibitors, phosphodiesterase 3 inhibitors, and monoclonal antibodies to the interleukin 1 receptor—offer additional hope for treatments that may prevent exacerbations in the future.
Background: The relevance of Aspergillus fumigatus in patients with cystic fibrosis (CF) not affected by allergic bronchopulmonary aspergillosis is unclear. Our aim was to
determine the effect of ...persistent infection with A fumigatus on pulmonary exacerbations and lung function in children with CF.
Methods: This was a retrospective cohort study of patients with CF followed at The Hospital for Sick Children from 1999 to 2006. Persistent
A fumigatus infection was defined as the presence of two or more positive sputum or bronchoalveolar cultures for A fumigatus in a given year. The primary outcome measure was the annual number of hospitalizations for pulmonary exacerbations.
Results: Two hundred thirty patients with CF were included in the analysis. The FEV 1 of patients persistently infected with A fumigatus was 3.61% ( P â¤.0001) lower during the study period compared with uninfected patients. There was a significant interaction between A fumigatus and Pseudomonas aeruginosa on lung function ( P =.0006). Patients not infected with either organism had the highest pulmonary function. Persistent A fumigatus infection (relative risk RR=1.94, P =.0002) and CF-related diabetes (RR=1.64, P =.028) were associated with an increased risk of pulmonary exacerbations requiring hospitalization, whereas there was no increased
risk of pulmonary exacerbations among patients with allergic bronchopulmonary aspergillosis (RR=1.02, P =.94). When adjusted for baseline pulmonary function, none of these variables were associated with a significantly increased
risk of pulmonary exacerbations, with only chronic A fumigatus infection trending toward significance (RR=1.40, P =.065).
Conclusions: Persistent A fumigatus infection is an independent risk factor for hospital admissions in patients with CF.
: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of ...expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.
: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.
: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations:
) a strong recommendation for the use of long-acting β
-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance;
) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year;
) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year;
) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy;
) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and
) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.
: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.
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