No abstract

Inhalation of hypertonic saline (HS) acutely enhances mucociliary clearance (MC) in both health and disease. In patients with cystic fibrosis (CF), repeated use of HS causes a sustained improvement in MC as well as clinical benefit. The pharmacodynamic duration of activity on MC may be an important determinant of its therapeutic potential in other airways diseases. Before moving toward testing the clinical benefits of HS for non-CF indications, we sought to assess the duration of pharmacodynamic effects of HS in healthy subjects by performing radiotracer clearance studies at baseline, 30-min post-HS administration, and 4-h post-HS administration. Indeed, acceleration of MC was observed when measured 30 min after HS inhalation. This acceleration was most pronounced in the first 30 min after inhaling the radiotracer in the central lung region (mean Ave30Clr = 15.5 vs. 8.6% for 30-min post-HS treatment vs. mean baseline, respectively, P < 0.005), suggesting that acute HS effects were greatest in the larger bronchial airways. In contrast, when MC was measured 4 h after HS administration, all indices of central lung region MC were slower than at baseline: Ave30Clr = 5.9% vs. 8.6% (P = 0.10); Ave90Clr = 12.4% vs. 16.8% (P < 0.05); clearance through 3 h = 29.4 vs. 43.7% (P < 0.002); and clearance through 6 h = 39.4 vs. 50.2% (P < 0.02). This apparent slowing of MC in healthy subjects 4-h post-HS administration may reflect depletion of airway mucus following acute HS administration.

Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, is implicated as a possible therapy for airway inflammation via induction of the transcription factor NF-E2-related factor 2 (NRF2). In this proof-of-concept clinical study, we show that supplementation of SFN with broccoli sprout homogenate in healthy human subjects did not induce expression of antioxidant genes or protect against neutrophilic airway inflammation in an ozone-exposure model. Therefore, dietary sulforaphane supplementation is not a promising candidate for larger scale clinical trials targeting airway inflammation.

In a prospective 2-year study, serological responses to selected pathogens were analyzed in 224 episodes of fever attributable to respiratory tract infection (51.8%) or of unknown source (48.2%) in 131 residents of two long-term-care facilities. A serological response was identified in 45 episodes (20.1%): Chlamydia pneumoniae (14 episodes), Haemophilus influenzae type b (1), influenza virus type A (14), respiratory syncytial virus (RSV;2), parainfluenza virus type 3 (7), C. pneumoniae and H. influenzae (3), C. pneumoniae and influenza virus type A (2), C. pneumoniae and RSV (1), and C. pneumoniae and parainfluenza virus type 3 (1). No serological responses to Chlamydia psittaci, Chlamydia trachomatis, parainfluenza virus types 1 and 2, influenza virus type B, or Mycoplasma pneumoniae were seen. Vaccination did not affect the duration of fever in those residents with serologically confirmed influenza A. Serologically confirmed C. pneumoniae infection was detected in 9.4% of all febrile episodes. Serological responses to a second agent were detected in 33% of the patients with C. pneumoniae infections, and these dual infections were associated with an underlying malignancy (P = .02). C. pneumoniae should be recognized as a potential pathogen when choosing empirical antimicrobial therapy for respiratory tract infection in residents of long-term-care facilities.