Therapeutic Advances in Respiratory Disease

Objective: To describe the approach to asthma exacerbations in a primary care centre in comparison with current guidelines and to ascertain the resolution of the episodes.

Methods: A cross-sectional, descriptive study was performed in asthmatic patients over 14 years old who were consulting for asthma exacerbations in a primary care centre during a 6-month period. The treatment given and the resolution obtained were evaluated.

Results: One hundred and twenty-three asthma exacerbations were registered, corresponding to 96 patients. A total of 74% were mild exacerbations, 24.4% moderate and 1.6% severe. The severity of asthma correlated directly with the severity of exacerbations. The frequency of resolution was 98.4%, with an average duration of medical attention of 30 min (SD 16.5). According to guidelines, 60.2% of the mild exacerbations were well treated, as were 26.7% of the moderate exacerbations and none of the severe episodes. Peak expiratory flow was measured in 54.5% of patients. In 82 cases (66.6%) salbutamol was given with a large-volume spacer chamber. Treatment after discharge was correct in 27.3% of the mild and 23.3% of the moderate exacerbations. A total of 23 (23.9%) patients presented more than one exacerbation during the study period.

Conclusions: Most exacerbations seen in primary care are mild. Administration of salbutamol was sufficient for the resolution of these exacerbations. However, treatment after discharge was not compliant with guidelines in most cases. The primary care team was able to resolve most of the asthma exacerbations.

Rationale: Previous studies have demonstrated that long-term low-dose macrolides are efficacious in cystic fibrosis (CF) and diffuse panbronchiolitis, two chronic neutrophilic airway diseases.

Aims: The aims of this study were to evaluate the efficacy and safety of low-dose neomacrolides as add-on therapy in patients with severe asthma and/or bronchiectasis and to identify predictors for therapeutic response.

Methods: In a retrospective observational cohort study, we examined 131 adult, non-CF patients with severe asthma and/or bronchiectasis, receiving low-dose neomacrolides as add-on treatment. Pulmonary function tests and symptom scores were assessed at baseline and after 3 to 8 weeks of therapy.

Results: After 3–8 weeks of treatment with low-dose neomacrolides, 108 patients were available for evaluation. In asthma patients (n = 47), pulmonary function tests and symptom scores improved significantly. Responders (≥7% forced expiratory volume in one second predicted [FEV₁%] improvement) were older (55 vs. 47 years; p = 0.042) and had a longer duration of asthma (29 vs. 9 years; p = 0.052). In patients with bronchiectasis only (n = 61), symptom scores improved significantly. Responders (≥60% symptom score improvement) were older (61 vs. 53 years; p = 0.004), more frequently male (53% vs. 27%; p = 0.043), and there was a nonsignificant trend towards higher high-resolution CT (HRCT) score for bronchiectasis in responders (6.4 vs. 4.6; p = 0.053). In multivariate logistic regression analysis, age and male gender were independent predictors for improvement in this group.

Conclusion: The results of this retrospective study suggest that neomacrolides may be useful as an add-on therapy in patients with severe asthma and/or bronchiectasis. Older age may predict good response in patients with severe asthma, whereas older age, male gender and a higher HRCT score for bronchiectasis may predict therapeutic response in patients with bronchiectasis only. Prospective controlled trials of neomacrolides in patients with severe asthma are needed to confirm these observations.

Refractory asthma not only has a significant effect on quality of life, but also imposes an economic burden on society. Increasing evidence suggests that there is a pathophysiologic interaction between infection and allergic disease in patients with severe or refractory asthma. Therapeutic trials of macrolides and azoles are being utilized in some patients with refractory asthma who fail to respond to standard therapy. In this article we review the definition of refractory asthma and the potential pathophysiologic interactions between infection and allergic disease. Emerging data suggest that microorganisms and their byproducts may be a therapeutic target in the therapy of patients with severe or refractory asthma.

Following a peak in asthma mortality in the late 1980s and early 1990s, we have been fortunate to see a substantial decrease in asthma deaths in recent years. Although most asthma deaths occur outside the hospital, near-fatal events are commonplace, with anywhere from 2–20% of patients with acute asthma admitted to intensive care, and 2-4% intubated for respiratory failure. Standard therapies for acute severe and near-fatal asthma include administration of systemic corticosteroids, and frequent or continuous inhaled beta agonists. Controversy remains regarding the optimal therapy of those who fail to respond to these initial treatments, those who remain at risk of acute respiratory failure, and patients requiring mechanical ventilation. There remain significant gaps in our knowledge regarding relative benefits of intravenous versus oral corticosteroids, intermittent versus continuous beta agonists, and the role of various adjunctive treatments including intravenous magnesium, systemic beta agonists, aminophylline, and helium-oxygen mixtures. Using models and radiolabeled aerosols, there is a greater understanding regarding effective administration of inhaled beta-agonists in ventilated patients. There is limited available evidence for treatment of near-fatal asthma, a fact reflected by the significant variability in asthma critical care practice. Much of the data guiding treatment in this setting has been generalized from studies of acute asthma in the ED and from general populations of hospitalized patients with acute asthma. This review will focus on pharmacologic approaches to life-threatening asthma by reviewing current guideline recommendations, reviewing the scientific basis of the guidelines, and highlighting gaps in our knowledge in treatment of refractory acute or near-fatal asthma.

Pleural disease in lung cancer can be benign or malignant with the latter carrying a grave prognosis. In this review, we describe and discuss the advances in pleural imaging, procedures, and biomarkers for the diagnosis of pleural diseases in lung cancer. Ultrasound and computed tomography are increasingly applied in the planning of pleural procedures to enhance diagnostic accuracy and safety whilst pleuroscopy gives excellent yield in excess of 93% in the evaluation of cytology negative pleural effusions. Invasion beyond the elastic layer of the visceral pleura upstages lung cancer, and may indicate a need for adjuvant chemotherapy. Biomarkers isolated from pleural fluid or tissue may aid in diagnosis and guide treatment in the future. Magnetic resonance imaging, positron emission tomography, narrow band imaging of the pleura and autofluorescence thoracoscopy are technologies that require further evaluation to better define their respective roles in the diagnostic algorithms of pleural diseases in lung cancer.

Multiple medical therapies have been developed for the treatment of pulmonary arterial hypertension (PAH) over the last decade and a half. Unfortunately, none of these medications is curative and the majority of patients develop disease progression despite treatment. Presently available medications target one of three known pathways that have been implicated in disease pathogenesis. The multiplicity of pulmonary vascular abnormalities identified in PAH provides the rationale for a therapeutic strategy that targets more than one mechanism at a time. Although a handful of studies have demonstrated clinical improvement in PAH patients who have a second medication added to stable background therapy in a randomized, placebo-controlled fashion, it is unclear whether the derived benefit is due to the combination of two therapies or merely the response to the new agent. This review discusses the rationale for combination therapy, critically reviews the findings of presently completed combination studies and outlines the need for new studies that are better designed to determine whether combination therapy is more efficacious than single agent therapies for the treatment of PAH.