ABSTRACT
Infection frequently causes exacerbations of chronic obstructive pulmonary disease (COPD). Mannose-binding lectin (MBL) is a pattern-recognition receptor that assists in clearing microorganisms. Polymorphisms in the MBL2 gene reduce serum MBL levels and are associated with risk of infection. We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility. Polymorphism frequency was determined by PCR-RFLP in 200 COPD patients and 104 smokers with normal lung function. Serum MBL was measured as mannan-binding activity in a subgroup of 82 stable COPD patients. Frequency of COPD admissions for infective exacerbation was ascertained for a 2-year period. The MBL2 codon 54 B allele reduced serum MBL in COPD patients. In keeping, patients carrying the low MBL-producing B allele had increased risk of admission for infective exacerbation (OR 4.9, P(corrected)=0.011). No association of MBL2 genotype with susceptibility to COPD was detected. In COPD, serum MBL is regulated by polymorphism at codon 54 in its encoding gene. Low MBL-producing genotypes were associated with more frequent admissions to hospital with respiratory infection, suggesting that the MBL2 gene is disease-modifying in COPD. MBL2 genotype should be explored prospectively as a prognostic marker for infection risk in COPD.
Subject(s)
Genetic Predisposition to Disease , Hospitalization , Mannose-Binding Lectin/analogs & derivatives , Mannose-Binding Lectin/genetics , Polymorphism, Genetic , Pulmonary Disease, Chronic Obstructive/genetics , Adult , Aged , Aged, 80 and over , Amino Acid Substitution/genetics , Female , Hospitalization/statistics & numerical data , Humans , Male , Mannose-Binding Lectin/blood , Middle Aged , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/epidemiologyABSTRACT
The effect of adding nebulised ipratropium bromide to bronchodilator treatment was studied in 20 patients with severe chronic airflow limitation. Maintenance theophylline with or without a steroid preparation was continued and comparison made between placebo, nebulised salbutamol, and a combination of nebulised salbutamol and ipratropium. Although the mean FEV1 values showed the combination to produce a small but significant increase in peak bronchodilatation over the effect of salbutamol alone, there were eight patients in whom no clinically useful improvement occurred. The remaining 12 patients did obtain clinically useful improvement in the magnitude or the duration of bronchodilatation (or both) as a result of the added ipratropium. The conclusion is that individual patients with chronic airflow limitation responded to the addition of nebulised ipratropium bromide in a variable way. Patients who could obtain additional benefit from ipratropium need to be identified by an appropriate reversibility study before its inclusion in their bronchodilator treatment.
Subject(s)
Atropine Derivatives/administration & dosage , Ipratropium/administration & dosage , Lung Diseases, Obstructive/drug therapy , Aerosols , Aged , Albuterol/therapeutic use , Clinical Trials as Topic , Double-Blind Method , Drug Therapy, Combination , Female , Forced Expiratory Volume , Humans , Lung Diseases, Obstructive/physiopathology , Male , Middle Aged , Random AllocationABSTRACT
A placebo controlled study compared the magnitude and duration of bronchodilatation produced by nebulised salbutamol (5 mg) and ipratropium (0.5 mg) singly and in combination in twenty patients with chronic bronchitis (mean baseline FEV1 was 33% predicted). The onset of action, of both nebulised salbutamol and ipratropium given singly, occurred within 15 min. Both agents produced a similar degree of bronchodilatation. In combination both the magnitude and duration of the bronchodilatation produced was significantly greater than with either agent alone.