Idiopathic pulmonary fibrosis (IPF) is a disease of the elderly with a mean age at presentation of 66 years. It is the most common type of idiopathic lung fibrosis, and the most lethal, with a median survival of 3 to 5 years after diagnosis. Abnormalities in fibroblast and humoral response mechanisms may play a role in the pathogenesis of fibrosis in IPF.

Clinical trials suggest that pirfenidone, an oral antifibrotic agent, N-acetylcysteine, an antioxidant and perhaps anticoagulation, may have some beneficial effect; however, large-scale studies are necessary for confirmation. Immunosuppression with corticosteroids likely does not confer benefit. Lung transplantation has been shown to improve survival in selected IPF patients. Comorbidities accompanying IPF include gastroesophageal reflux, sleep disturbance, pulmonary arterial hypertension, and coronary artery disease amongst others, and ought to be promptly recognized and managed appropriately.

While the US Food and Drug Administration has not currently approved any treatments for IPF, patients with IPF should continue to be strongly encouraged to enroll in ongoing clinical trials for this devastating disease.

Cigarette smoking is the principal cause of chronic obstructive lung disease (COPD), especially emphysema, which is characterized by alveolar wall destruction and airspace enlargement. Apoptosis of lung structural cells is involved in the pathogenesis of COPD. Xanthine derivatives (aminophylline or theophylline) have been used for the treatment of COPD as a bronchodilator. But, the effects of xanthine derivatives on apoptosis of the lung structural cells remains poorly understood, even though it is known that theophylline protects against ultraviolet irradiation-induced cell death in corneal epithelial cells. This study was designed to determine whether aminophylline would protect against cigarette smoke extract (CSE)-induced apoptosis in lung fibroblasts.

We demonstrated that aminophylline protected against apoptosis of MRC-5 cells at a relatively lower therapeutic range (10 ug/ml), resulting in a significant increase in cell viability occurring at 20% concentration after 8 hr exposure. Annexin staining decreased from 68 ± 4% of the control to 12 ± 2% of aminophylline (10 ug/ml) pre-treatment after 20% CSE exposure for 12 hr (p<0.05). Aminophylline decreased caspase 3 and 8 activity and nuclear condensation or fragmentation in MRC-5 cells after exposing 20% CSE for 12 hr compared with control and high levels of aminophylline (> 50 ug/ml) pre-treatment. These findings suggest that aminophylline protected against apoptosis of MRC-5 cells through the inactivation of caspase 3 and 8, and could be an effective agent to reduce cigarette smoking-induced lung structural cell apoptosis.

PURPOSE:: We sought to quantify the impact of respiratory muscle and lower extremity strength on exercise capacity and lower extremity function (LEF) in patients with chronic obstructive pulmonary disease (COPD).

METHODS:: In 828 persons with COPD, we assessed the impact of reduced respiratory (maximum inspiratory pressure, MIP) and lower extremity muscle strength (quadriceps strength, QS) on exercise capacity (6-minute walk test, 6MWT), and LEF (short physical performance battery). Multiple regression analyses taking into account key covariates, including lung function and smoking, tested the associations between muscle strength and exercise and functional capacity.

RESULTS:: For each 0.5 SD decrement in QS, men walked 18.3 m less during 6MWT (95% confidence interval [CI], -24.1 to -12.4); women 25.1 m less (95% CI, -31.1 to -12.4). For each 0.5 SD decrement in MIP, men walked 9.4 m less during 6MWT (95% CI, -15.2 to -3.6); women 8.7 m less (95% CI, -14.1 to -3.4). For each 0.5 SD decrease in QS, men had a 1.32 higher odds (95% CI, 1.11-1.15) of poor LEF; women had a 1.87 higher odds (95% CI, 1.54-2.27). Lower MIP (per 0.5 SD) was associated with increased odds of poor LEF in women (odds ratio = 1.18; 95% CI, 1.00-1.39), but not in men (odds ratio = 1.10; 95% CI, 0.93-1.31).

CONCLUSIONS:: In COPD, reduced respiratory and lower extremity muscle strength are associated with decreased exercise and functional capacity. Muscle weakness is likely an important component of impairment and disability in patients with COPD.

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by chronic lung and sinus disease, impaired mucociliary clearance (leading to recurrent pulmonary infection), pancreatic insufficiency, elevated sweat chloride levels and male infertility.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel in the plasma membrane of epithelial cells lining the lung, pancreas, liver, intestines, sweat duct, and the epididymis. Genetic mutations in CFTR affect its synthesis, processing, and transport to the plasma membrane and/or impede its function as a chloride channel and conductance regulator. Research is proceeding on multiple fronts including inhalational agents, anti-inflammatory treatments, and pancreatic replacement therapies. Furthermore, improved understanding of the molecular mechanisms that lead to CFTR dysfunction has stimulated the design of therapeutic strategies aimed at restoration of CFTR function, or "protein repair therapy". Recent clinical trials have shown these interventions have the ability to restore some level of CFTR function in vivo.

This review will provide an overview of recent clinical trials that investigate new therapeutic approaches in CF designed to treat chronic respiratory infection, reduce inflammation, and improve pancreatic enzyme supplementation as well as trials addressing the greatest therapeutic challenge - restoring the function of the CFTR protein.