BACKGROUND:Recent studies demonstrate that genetic variations in the human beta(2)-adrenergic receptor (beta(2)AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain.OBJECTIVE:We determined frequencies of these polymorphisms to explore the association between beta(2)AR haplotypes and asthma diagnosis and phenotype.METHODS:This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at beta(2)AR was identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between beta(2)AR haplotype status and asthma diagnosis.RESULTS:A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the "Gly16 allele without Glu27" (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6).CONCLUSIONS:Variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma.

This randomised, multicentre, parallel-group study compared the clinical efficacy and ease of handling of two dry powder inhalers delivering the long-acting beta 2-agonist formoterol. After run-in, 200 asthmatics on treatment with inhaled corticosteroids and still presenting with suboptimal asthma control were randomised to receive 12 micrograms formoterol twice daily via either the Aerolizer inhaler (Foradil Aerolizer) or the Turbuhaler inhaler (Oxis Turbuhaler) for four weeks. Study variables included the mean morning pre-medication peak expiratory flow (PEF) during the last seven days of treatment and the correct inhaler handling according to inhaler-specific checklists. The mean difference in the effect on morning pre-medication PEF was 13.86 l/min in favour of formoterol via the Aerolizer inhaler (90% confidence interval 2.50, 25.21) in the intent-to-treat population. Eighty-six per cent of the patients under treatment with formoterol via the Turbuhaler inhaler performed correctly all the essential inhalation manoeuvres, whereas 98% of those on the Aerolizer inhaler did so. These results strongly suggest similar clinical efficacy with twice daily treatment of formoterol 12 micrograms metered dose delivered either by the Aerolizer, or the Turbuhaler device. They also suggest that handling the Aerolizer is easier than that of the Turbuhaler.

STUDY OBJECTIVES To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. DESIGN A randomized, double-blind, double-dummy, two-period, crossover clinical trial. SETTING Twenty-four clinics and university medical centers in nine countries. PATIENTS One hundred seventy-two patients with baseline FEV(1) < or = 65% predicted, with FEV(1) reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. INTERVENTIONS Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg qid for 3 weeks, or vice versa. MEASUREMENTS AND RESULTS Efficacy end points included morning premedication peak expiratory flow (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV(1) measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV(1) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042). The safety profile of the two treatments was comparable. CONCLUSIONS In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.

A study was conducted in 14 patients with pericardial syndrome after pulmonary embolism. The role of right ventricular myocardial injury and noncardiogenic pulmonary edema in this syndrome is considered and its existence is established.

To test the efficacy of intrapleural fibrinolytic therapy in patients with loculated pleural effusions, we conducted an open, prospective, and multicenter trial among five hospitals in Mexico. We enrolled patients with hemothorax or empyema, clotted and/or loculated, that was not resolved through conventional pleural drainage with chest tube and antibiotics in patients with empyema, All patients received repeated doses of 250,000 IU of streptokinase through chest tube. Effectiveness criteria were before and after intrapleural streptokinase (IPSK) drainage, and poststreptokinase radiographic and respiratory function test improvement, Forty-eight patients were studied; there were 30 patients with empyemas, 14 with hemothorax, and 4 patients with malignant pleural effusions without lung trapping, Successful fibrinolysis was obtained in 44 patients, with complete resolution of the pleural collection and adequate radiologic and spirometric improvement. In three of four patients with multiloculated malignant hemothorax with high-yielding pleural drainage, IPSK allowed successful lysis of loci and an adequate pleurodesis was achieved. Only four patients required surgical treatment. The overall success rate in our series was 92%, similar to previous reports. The results in this first prospective and multicentric trial suggest that intrapleural fibrinolysis is an effective and safe adjunctive treatment in patients with heterogeneous pleural coagulated and loculated collections to restore the pulmonary function assessed by respiratory function tests and can obviate surgery in most cases.

Among 195 patients with pulmonary embolism admitted to our hospital, three men and three women, 16 to 65 years old, developed a pericardial syndrome five to 15 days after the onset of pulmonary embolism and infarction. Other known causes of pericarditis were ruled out by clinical history and ancillary methods. The six patients had a pericardial rub, fever, anemia, leukocytosis, and increasing sedimentation rate; four had a pericardial effusion; two had a pleural effusion. One patient, with coexisting heart disease, died after another episode of pulmonary embolism; in the other five, oral corticosteroids induced complete remission of the pericardial syndrome. This type of pericarditis deserves wider recognition.