Adverse effects of brompheniramine on pulmonary function in a subset of asthmatic children

The role of antihistamines in the therapy of bronchial asthma has remained controversial. Early studies suggested a possible aggravation of symptoms but more recent studies implied their safety. Ten asthmatic children who reported a feeling of chest tightness and subsequent wheezing after taking a preparation containing brompheniramine maleate were studied in addition to 10 control asthmatic children who reported no such adverse effect. All children were only intermittently symptomatic and did not require constant bronchodilator therapy. They were well at the time of the study. Challenges were performed with the antihistamine alone (4 mg of brompheniramine maleate), a decongestant-antihistamine combination (4 mg of brompheniramine maleate, 5 mg of phenylephrine HCl, 5 mg of phenylpropanolamine HCl), and a placebo. Results indicated a statistically significant decrease in pulmonary function in the study children when challenged with the antihistamine and decongestant-antihistamine preparation but not when challenged with the placebo. The 10 control asthmatic children did not exhibit this phenomenon and premedication with theophylline prevented the decrease in pulmonary function in the study group. Therefore a subset of asthmatic children does appear to exist in whom the use of an antihistamine may be harmful.     

The immediate effects of cortisol on pulmonary function in normals and asthmatics

We investigated short-term effects of corticosteroids on airway caliber, measured by spirometry and body plethysmography, over a period of 6 hr after an intravenous bolus of cortisol (8 mg/kg) or saline placebo was administered in a double-blind crossover format comparing 10 normal and nine asymptomatic unmedicated asthmatics. After 6 hrs isoproterenol (240 μg) was administered to compare the effects of cortisol with a β-agonist bronchodilator. Serum cortisol levels remained >100 μg/dl after cortisol and normal after placebo. Cortisol had no effect on pulmonary function except for a trend of improved flows and decreasing ratios of residual volume to total lung capacity in asthmatics that was not significant at 6 hr. Isoproterenol resulted in immediate improvement in specific conductance and flows in both groups; no interaction with cortisol was seen. We conclude that cortisol had no short-term effect on airway caliber in normals, at best a slowly evolving effect in asymptomatic unmedicated asthmatics, and no interaction with the bronchodilator effects of a maximal dose of isoproterenol in these groups.     

The short-term bronchodilator effects of fenoterol and ipratropium in asthma

We studied the bronchodilator effects of inhaled fenoterol, a relatively selective beta-2 adrenergic agent, and ipratropium an anticholinergic drug, singly and in combination in 10 patients with asthma. The period of observation was 6 hr after aerosol administration. The six drug regimens used were fenoterol 100 micrograms, fenoterol 200 micrograms fenoterol 50 micrograms combined with 20 micrograms of ipratropium, fenoterol 100 micrograms combined with 40 micrograms of ipratropium, 40 micrograms of ipratropium, and placebo. Measurements consisted of spirometry with determination of forced expiratory volume in one second (FEV1), maximal expiratory flow at 50% of vital capacity (V50), specific airway conductance, lung volumes, and heart rate. Bronchodilation with regimens containing fenoterol was rapid, with 75% of the maximum response achieved by 5 min, while the peak effect of ipratropium was delayed for 1 to 2 hr. Fenoterol 100 micrograms produced approximately half the degree of improvement in FEV1 and V50 compared with 200 micrograms of fenoterol. The addition of 40 micrograms of ipratropium to 100 micrograms of fenoterol resulted in bronchodilation equivalent to 200 micrograms fenoterol and was associated with a more prolonged effect than fenoterol 100 micrograms. Tremor was observed in two-subjects inhaling fenoterol 200 micrograms but was not observed with any other regimen. It is concluded that the combination of inhaled ipratropium and fenoterol is an effective bronchodilator in asthma, achieving efficacy similar to that of fenoterol alone but with fewer side effects.     

Effects of influenza vaccination on clinical outcomes of chronic obstructive pulmonary disease: A systematic review and meta-analysis

PurposeInfluenza is a threat to patients with chronic obstructive pulmonary disease (COPD), influenza vaccination help to reduce incidence of influenza infection, however, whether it is beneficial to COPD patients in clinical outcomes lacks for evidence due to limited studies and participations.MethodsWe searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Science and Technology Journal Database (CSTJ) to retrieve eligible studies regardless of study design published before August 2020, and conducted meta-analysis with odds ratio (OR) and mean difference (MD). The quality of included studies and pooled evidences were assessed. Narrative summaries were provided where data were insufficient for meta-analysis.Results2831 COPD patients were included, the pooled results showed that influenza vaccination reduced the exacerbations (P = 0.0001) and trends of hospitalizations (P = 0.09) in COPD patients. Further subgroup analysis showed that the reduction of exacerbations and hospitalizations were significant in patients with FEV₁<50 % predicted (P = 0.01 and P < 0.0001 respectively), but not in those with FEV₁≥50 % predicted (P = 0.23 and P = 0.76 respectively). No significant effect of influenza vaccination on all-cause mortality was observed.ConclusionsOur findings support a protective role of influenza vaccination in COPD patients, a yearly influenza vaccination should be strongly recommended for all COPD patients, especially those with severe airflow limitation, to reduce possible influenza infection, and thus associated exacerbations and hospitalizations.     

Selective subsensitization of beta-adrenergic receptors in central airways of asthmatics and normal subjects during long-term therapy with inhaled salbutamol

In five subjects with mild asthma and in five normal subjects, we determined the effect of a 4 wk course of inhaled salbutamol (albuterol), 200 μg q.i.d., on (I) acute bronchodilator responsiveness, (2) bronchial sensitivity to inhaled histamine, (3) beta-adrenergic protection against histamine-induced bronchospasm, and (4) beta-receptor density of peripheral blood lymphocytes. We observed a diminution in central airway bronchodilator responsiveness (as measured by airway conductance responses) to acutely inhaled salbutamol and to subcutaneous terbutaline in both groups of subjects, although only the response to subcutaneous terbutaline was statistically significant (p < 0.02). On the other hand, no impairment of small airway bronchodilator responsiveness was noted in either group of subjects when responses were measured as partial expiratory flow rates at 60% below total lung capacity. These findings suggest the development of selective subsensitization of beta-receptors in the larger central airways, where a proportionately greater amount of the inhaled beta-agonist aerosol would necessarily be deposited. A greater loss of protection against histamine-induced bronchospasm was seen in asthmatics than in normals (approximately twofold), although the difference was not significant. A modest but not significant reduction in peripheral blood lymphocyte beta-receptor density was observed by the end of the 4 wk treatment period. The possibility that the observed changes in bronchodilator responsiveness might influence the morbidity and mortality associated with bronchial asthma is discussed.     

Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid,budesonide

The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated. Budesonide, a topically active corticosteroid like beclomethasone dipropionate, was given q.i.d. or b.i.d., in the morning or A.M./P.M., at doses of 400, 800, and 1600 μg/day. Each patient (n = 34) took every treatment combination for 2 wk. The antiasthmatic and systemic effects, measured by changes in peak expiratory flow rate (PEFR), blood eosinophils, and serum cortisol levels increased approximately linearly on log dose budesonide (p < 0.0005). Systemic effects of the drug were nonsignificant at low dosage. At high dosage, morning dosing conserved hypothalamic-pituitary-adrenal function, but at the cost of a marginal reduction in efficacy (Δ PEFR, p =0.12). Halving the dose frequency reduced the antiasthmatic potency of the drug, i.e., PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage (p = 0.002). This effect was not evident when asthma was in remission but became so with asthma in relapse. Overall, the q.i.d. A.M./P.M. regimen showed the best risk-benefit relationships. The data indicate (I) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drug's long-term efficacy are likely to lead to the reverse effect, (2) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day, and (3) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs (or apparent risk) by simply increasing dosing frequency. These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma.