A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis

Objectives: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. Method: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. Results. There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P < .05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. Conclusion: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.

Successful treatment of post-influenza pseudomembranous necrotising bronchial aspergillosis with liposomal amphotericin, inhaled amphotericin B, gamma interferon and GM-CSF

A case of aspergillus tracheobronchitis following influenza A infection in an immunocompetent 35 year old woman is described that required prolonged mechanical ventilation for airways obstruction. Treatment included liposomal amphotericin, inhaled amphotericin, gamma interferon and GM-CSF. Liposomal amphotericin therapy was associated with reversible hepatosplenomegaly. Inhaled corticosteroids with continued antifungal therapy were used for the management of severe recurrent airway obstruction. After a prolonged course of treatment she survived with fixed airways obstruction unresponsive to corticosteroids.

Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function

1 Hypoxic pulmonary hypertension in rats (10% O-2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2 Perindopril (30 mg kg(-1) d(-1)) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3 Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries (50 mu m 0.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30-100 and 101-500 mu m o.d.). Perindopril 10 and 30 mg kg(-1) d(-1) attenuated remodelling in vessels less than or equal to 100 mu m (lungs and histology), 30 mg kg(-1) d(-1) was effective in vessels 101-500 mu m but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg(-1) d(-1) was without effect. 4 Perindopril (30 mg kg(-1) d(-1)) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5 We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.

Vitamin A is associated with the inflammatory marker CRP in cystic fibrosis

We have observed that vitamin A levels, deficient in patients with severe disease, returned to normal post lungtransplant independent of oral supplementation or pancreatic sufficiency. We hypothesised that vitamin A is associated with disease severity and the inflammatory marker C-related peptide (CRP). Data from RCH paediatric and TPCH adult CF clinic subjects (ns138 CF, 138 control, aged 5–56 yr), who had participated in a study of bone mineral density (BMD) in which vitamins A, E, D, and CRP, height, weight and lung function had been measured was used. Groups were compared using t- or Wilcoxon-tests, and predictors of vitamin A examined usingmultiple regression. Vitamin A was lower in CF subjects (1.23"0.5 vs. 1.80"0.6 mmolyl, P-0.0001), increasingwith age in paediatric subjects but to a lesser extent in the CF group (Ps0.0007). CRP was correlated with age (rs0.6, P-0.0001). FEV1% predicted (FEV) (57.93"23.0 vs. 70.63"21.8, Ps0.0014), weight z-score (WTZ) (y0.76"0.9 vs. y0.12"1.0, Ps0.0002), lumbar spine BMD z-score (y1.08"1.3 vs. y0.50"1.2, Ps0.009) were lower, and CRP higher (median 7.0, IQR 2–4 vs. median 1.0, IQR 1–3 mgy l, P-0.0001) in vitamin A insufficient CF subjects (61 insufficient vs. 71 sufficient). In all subjects, control status (P-0.0001), WTZ (Ps0.02), vitamin E (Ps 0.0003), CRP (Ps0.001), 1,25 dihydroxy vitamin D (1,25 vit. D) (Ps0.0007), and child, adolescent or adult grouping (all P-0.0001) were predictive of vitamin A. In the CF group, CRP (Ps0.01), Vitamin E (P-0.0001) and 1.25 vit. D (Ps 0.006), but not FEV, were predictive. The normal increase in vitamin A with age was not observed in CF subjects, who had lower levels at any age. This failure of normal increase in vitamin A had a consistent association with increasingCRP , supportingthe hypothesis that increased inflammation may result in increased vitamin A consumption.