E. Rand Sutherland

Airway inflammation in chronic obstructive pulmonary disease: Comparisons with asthma

Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of expiratory airflow limitation caused by chronic inflammation of the airways and lung parenchyma. The airway inflammatory response in COPD is initiated by smoking in the overwhelming majority of cases, and chronic exposure to cigarette smoke initiates a series of events that causes damage to central airways, peripheral airways, and terminal airspaces, leading to physiologic and clinical abnormalities. Although COPD shares some clinical features with asthma, another prevalent airway inflammatory disease, there are distinct differences in the phenotypic characteristics of airway inflammation between COPD and asthma. The eosinophil is the most prominent inflammatory cell in asthma, with mast cells, lymphocytes, and macrophages playing important but less prominent roles. In COPD the cellular composition of the airway inflammatory infiltrate differs, with neutrophils, macrophages, and lymphocytes assuming prominence and the eosinophil playing a minor role, except in the setting of exacerbations. The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy.

Elevated serum melatonin is associated with the nocturnal worsening of asthma

BACKGROUNDnIncreased airway inflammation at night contributes to the nocturnal worsening of asthma. In vitro studies have shown exogenous melatonin to be pro-inflammatory in asthma, but it is unknown whether endogenous melatonin levels are a controller of airway inflammation in nocturnal asthma.nnnOBJECTIVEnOur aim was to determine 24-hour patterns of serum melatonin and their relationship to overnight decline in physiology in subjects with nocturnal asthma, non-nocturnal asthma, and in healthy controls.nnnMETHODSnObservational study of pulmonary physiology and melatonin levels in patients with nocturnal asthma (n = 7), non-nocturnal asthma (n = 13), and healthy controls (n = 11). Subjects maintained a constant sleep-wake regimen for 7 days. On day 8, serum melatonin was measured every 2 hours by radioimmunoassay and analyzed by cosinor modeling. The correlation between serum melatonin levels and overnight change in spirometry was evaluated by Spearmans rank correlation analysis.nnnRESULTSnIn subjects with nocturnal asthma, peak melatonin levels were significantly elevated compared with healthy controls (67.6 +/- 5.0 pg/mL versus 53.5 +/- 4.0 pg/mL, P =.03). Melatonin acrophase was delayed in nocturnal asthma (02:54 versus 01:58 in healthy controls, P =.003, and 02:15 in non-nocturnal asthma, P =.01). In subjects with nocturnal asthma, increasing melatonin levels were significantly and inversely correlated with overnight change in FEV(1) (r = -.79, P =.04), a relationship that was not observed in non-nocturnal asthma or healthy controls.nnnCONCLUSIONSnNocturnal asthma is associated with elevation and phase delay of peak serum melatonin levels. Elevated melatonin levels might contribute to the pathogenesis of nocturnal asthma.

Atypical bacterial pneumonia and asthma risk

The role of respiratory infections in asthma is poorly understood. Atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae are present in the lower airways of approximately 50% of asthmatics. This study tested the hypothesis that early life community‐acquired pneumonia caused by Mycoplasma pneumoniae or Chlamydia pneumoniae is associated with increased asthma prevalence. Thirty‐five subjects with a history of community‐acquired pneumonia (22 due to atypical bacteria, 13 due to nonatypical pathogens) were evaluated by questionnaire 7–9 years after the episode of pneumonia. Subjects with a history of either typical or atypical pneumonia demonstrated increased asthma prevalence. Current or past asthma prevalence was 55% in subjects with atypical bacterial pneumonia and 61.5% in subjects with nonatypical bacterial pneumonia. Significant between‐group differences were not demonstrated with regard to asthma prevalence (risk ratio = 0.89; 95% confidence interval = 0.49–1.61), current bronchodilator use [1.18 (0.44–3.17)], and family history of atopy [1.18 (0.73–1.91)], or asthma [1.63 (0.68–3.88)]. These data suggest that atypical bacterial pneumonia confers a risk of asthma similar to that seen with nonatypical bacterial pneumonia. Prospective studies are warranted to more fully evaluate the importance of atypical bacterial pneumonia as an asthma risk factor.

Distal lung inflammation in asthma

OBJECTIVEnTo review the role of distal lung inflammation in asthma.nnnDATA SOURCES AND STUDY SELECTIONnSelected peer-reviewed research publications retrieved from MEDLINE search. Search was restricted to English-language publications only. Included articles were selected for their relevance to pathophysiology, diagnosis, and treatment. Bibliographies of selected papers served as an additional source of considered publications.nnnRESULTSnInflammation in the small airways and alveolar tissue plays an important role in the clinical manifestations of asthma. Diagnostic modalities such as transbronchial biopsy and evolving radiologic techniques such as high-resolution computed tomography are improving our ability to evaluate this portion of the lung. New ultra-fine particle size metered-dose inhalers and oral agents such as cysteinyl leukotriene receptor antagonists offer new opportunities for treating small airways inflammation and need to be fully evaluated for their ability to target and treat distal lung inflammation.nnnCONCLUSIONSnDistal lung inflammation is an important component of airway inflammation in asthma. New modalities for evaluating distal airway inflammation and for targeting the distal lung with inhaled and systemic drugs are rapidly expanding our knowledge of the clinical importance of distal lung inflammation and may ultimately be of critical importance in asthma therapy.