Long-term macrolide treatment of chronic inflammatory airway diseases: risks, benefits and future developments.

Macrolide antibiotics were discovered over 50 years ago and following their use as antimicrobials it became apparent that this group of antibiotics also possessed anti-inflammatory properties. Subsequent clinical trials showed benefits of macrolides as long-term adjuncts in the treatment of a spectrum of chronic inflammatory respiratory diseases, particularly diffuse panbronchiolitis, cystic fibrosis, post-transplant bronchiolitis obliterans and more recently chronic obstructive pulmonary disease (COPD). The evidence for efficacy of macrolides in the long-term treatment of chronic asthma and bronchiectasis is less well established. The mechanism(s) of action of macrolides in the treatment of these diseases remains unexplained, but may be due to their antibacterial and/or anti-inflammatory actions, which include reductions in interleukin-8 production, neutrophil migration and/or function. Macrolides have additional potentially beneficial properties including anti-viral actions and an ability to restore corticosteroid sensitivity. The increased prescribing of macrolides for long-term treatment could result in the development of microbial resistance and adverse drug effects. New macrolides have been developed which do not possess any antimicrobial activity and hence lack the ability to produce microbial resistance, but which still retain immunomodulatory effects. Potentially novel macrolides may overcome a significant barrier to the use of this type of drug for the long-term treatment of chronic inflammatory airway diseases.

Parenchymal emphysema measured by CT lung density correlates with lung function in patients with bullous disease.

In subjects with chronic obstructive pulmonary disease (COPD) computed tomographic (CT) lung density correlates with direct pathological measurements of the size of the distal airspaces, as well as with measurements of airflow limitation and impairment of the diffusing capacity. Thus, CT lung density can be used to quantify emphysema in life. We wanted to assess the use of CT scanning to detect and measure the extent of bullous lung, and to quantify the severity of emphysema in the non-bullous areas of the lungs. In patients with bullous emphysema (21 males and 2 females; aged 31-69 yrs; forced expiratory volume in one second (FEV1) 14-84% predicted; volume corrected diffusing capacity of the lungs for carbon monoxide (DLCO/VA) 17-114% predicted). CT lung density was measured in electromagnetic imaging (EMI) units. The extent of bullous emphysema correlated poorly with all respiratory function measurements. In contrast, the severity of emphysema in the non-bullous parts of the lungs, expressed as either the mean EMI number, or the EMI number of the lowest 5th percentile of the CT lung density histogram, correlated well with measurements of airflow limitation and diffusing capacity. Our findings, thus, suggest that in patients with bullae the major determinant of respiratory function is the severity of the emphysema in non-bullous lung, and that the extent of the bullae has less functional importance.(ABSTRACT TRUNCATED AT 250 WORDS)