Cigarette smoking and asthma interact to induce important adverse effects on clinical, prognostic and therapeutic outcomes. This review examines recent evidence on the harmful effects of smoking in asthma, possible underlying inflammatory mechanisms for this altered response, management options for these patients and potential future therapeutic directions. Active smokers, particularly females, are at risk of developing asthma.

Prevalence rates for smoking in asthma are relatively close to those found in the general population. Smokers with asthma experience worse asthma control than non-smokers with asthma. Mechanisms for the adverse effects of smoking in asthma include altered airway inflammation and corticosteroid insensitivity. Quitting smoking can improve symptoms and lung function, but the low rates of smoking cessation highlights the need for improved strategies for managing these patients.

Clinical trials assessing new therapies for asthma need to enrol smokers to identify treatments that are effective in the asthma smoking phenotype.

This systematic review and meta-analysis sought to investigate if asthma exacerbations, oral corticosteroid use, or asthma severity are associated with prematurity and intrauterine growth restriction Cohort studies published between 1975 and March 11, 2012 were considered for inclusion.

138 publications were identified for possible inclusion, and 9 papers met the inclusion criteria, by reporting perinatal outcomes of interest (low birth weight (<2500 gm), preterm birth (< 37 weeks gestation unless otherwise stated), and small for gestational age (<10th percentile for gestational age and sex) in groups of asthmatic patients stratified by history of exacerbations, oral corticosteroid use, or asthma severity.

Maternal asthma exacerbations and oral corticosteroid use had a significant effect on outcomes including: low birth weight (RR3.02, 95%CI[1.87,4.89]) and RR 1.41,95%CI[1.04,1.93], respectively) and preterm delivery (RR 1.54, 95%CI[0.89,2.69] and (RR 1.51,95%CI[1.15,1.98], respectively). Moderate to severe asthma during pregnancy was associated with an increased risk of small for gestational age (RR 1.24, 95%CI[1.15,1.35]) and low birth weight (RR 1.15,95%CI[1.05,1.26]) infants.

These data suggest that asthma exacerbations, oral corticosteroid use, or asthma severity defined as moderate to severe may be associated with preterm delivery, low birth weight, and small for gestational age. Further studies on the effect of maternal asthma control on perinatal outcomes are warranted.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective.

OBJECTIVES: Primary objective: to determine if treatment with mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both.Secondary objectives: to determine if mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with mucolytics.

SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012.
SELECTION CRITERIA: We included randomised studies that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis.

DATA COLLECTION AND ANALYSIS: The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis.

MAIN RESULTS: Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants.

AUTHORS' CONCLUSIONS: In participants with chronic bronchitis or COPD, treatment with a mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

Despite exacerbations of chronic obstructive pulmonary disease (COPD) being both common and often fatal, accurate prognostication of patients hospitalised with an exacerbation is difficult. For exacerbations complicated by pneumonia, the CURB-65 prognostic tool is frequently used but its use in this population is suboptimal.

METHODS: Consecutive patients hospitalised with an exacerbation of COPD were recruited. Admission clinical data and inhospital death rates were recorded. Independent predictors of outcome were identified by logistic regression analysis and incorporated into a clinical prediction tool.

RESULTS: 920 patients were recruited: mean (SD) age was 73.1 (10.0) years; 53.9% were female subjects; mean (SD) forced expiratory volume in one second was 43.6 (17.2) % predicted; and 96 patients (10.4%) died in hospital. The five strongest predictors of mortality (extended MRC Dyspnoea Score, eosinopenia, consolidation, acidaemia, and atrial fibrillation) were combined to form the Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial Fibrillation (DECAF) Score. The Score, which underwent internal bootstrap validation, showed excellent discrimination for mortality (area under the receiver operator characteristic curve =0.86, 95% CI 0.82 to 0.89) and performed more strongly than other clinical prediction tools. In the subgroup of patients with coexistent pneumonia (n=299), DECAF was a significantly stronger predictor of mortality than CURB-65.

CONCLUSIONS: The DECAF Score is a simple yet effective predictor of mortality in patients hospitalised with an exacerbation of COPD and has the potential to help clinicians more accurately predict prognosis, and triage place and level of care to improve outcome in this common condition.