Maternal smoking during pregnancy decreases Wnt signalling in neonatal mice

MJ Blacquiere, W Timens, A van den Berg, M Geerlings… - Thorax, 2010 - thorax.bmj.com
MJ Blacquiere, W Timens, A van den Berg, M Geerlings, DS Postma, MN Hylkema
Thorax, 2010thorax.bmj.com
Colonisation with Pseudomonas aeruginosa is a feature of bronchiectasis and is associated
with more severe disease and lower quality of life. 1 Nebulised colomycin, a polymixin,
bactericidal antibiotic with potent activity against most Gram-negative organisms, including P
aeruginosa, is frequently employed in these patients, but evidence is lacking for this
approach. We have retrospectively assessed the efficacy of nebulised colomycin in P
aeruginosa-colonised patients receiving a minimum of 6 months treatment. Patients who …
Colonisation with Pseudomonas aeruginosa is a feature of bronchiectasis and is associated with more severe disease and lower quality of life. 1 Nebulised colomycin, a polymixin, bactericidal antibiotic with potent activity against most Gram-negative organisms, including P aeruginosa, is frequently employed in these patients, but evidence is lacking for this approach. We have retrospectively assessed the efficacy of nebulised colomycin in P aeruginosa-colonised patients receiving a minimum of 6 months treatment. Patients who received concomitant prophylactic macrolide treatment for> 4 weeks were excluded. Bronchiectasis was confirmed in all patients by standard high-resolution CT criteria, and all received nebulised colomycin 1e2 megaunits twice daily through a standard jet nebuliser and compressor. The annualised frequency of hospital admissions, infective exacerbations requiring rescue antibiotics and sputum positivity for P aeruginosa per patient, prior to, and while on, colomycin treatment was compared. Forced expiratory volume in 1 s (FEV1) and self-reported sputum volume within 6 months of starting treatment and most recent on treatment were also compared. The data were analysed by nonparametric Wilcoxon test (table 1). Nineteen patients (9 males/10 females), mean age 66 years, were assessed between January 2000 and April 2007. Four patients had idiopathic disease and 15 disease of known cause. The mean length of data collection before commencing colomycin was 23.6 months and the mean duration on treatment was 21.2 months (range 6e39months) with 17 patients still on treatment at assessment (two patients discontinued treatment, one erroneously and one due to lack of efficacy). Only one previous study has interrogated the role of inhaled colomycin in this patient group. Steinfort et al2 retrospectively reviewed the efficacy of nebulised colomycin in 18 patients with chronic bronchial sepsis (14 with bronchiectasis) of whom 14 were colonised with P aeruginosa. There was a significant attenuation in decline in FEV1 and forced vital capacity (FVC), and an improvement in quality of life. P aeruginosa was eradicated in three patients but admission and exacerbation frequency were not assessed. Inhaled colomycin is frequently employed in patients with cystic fibrosis chronically colonised with P aeruginosa, but there is little evidence to support this. One study, involving 115 patients comparing inhaled colomycin with tobramycin over 4 weeks, demonstrated a significant decrease in the sputum P aeruginosa density with both treatments but a significant improvement in FEV1 in the tobramycin group only. 3 Several studies have assessed the efficacy of nebulised tobramycin in P aeruginosa-colonised patients with non-cystic fibrosis bronchiectasis. 4 5 Tobramycin consistently reduced sputum P aeruginosa density with eradication rates of 13e35%, but resistance emerged in 7e11% of patients. The only study addressing exacerbations demonstrated a significant reduction in admission, but not exacerbation, frequency. 5 Both studies showed a non-significant decrease in FEV1 on treatment, probably due to increased bronchospasm, with drug intolerance in up to 10% mainly due to airway symptoms.
In conclusion, nebulised colomycin appeared to reduce exacerbation frequency, hospitalisation, sputum P aeruginosa positivity and sputum volume in P aeruginosa-colonised patients with bronchiectasis and was well tolerated. These results are encouraging in this severely affected patient group and strengthen the need for a prospective, adequately powered, randomised controlled trial to investigate the efficacy of this treatment further.
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