Position statement: asthma in Latin America. IS short-acting beta-2 agonist helping or compromising asthma management?

In Latin-America, with 603 million inhabitants, the average prevalence of asthma is estimated at 17%, but with wide fluctuations, ranging from 5% in some cities (Mexico) to 30% in Costa Rica. The risk of severe exacerbations seems to be higher in Latin America compared with other regions. A majority of patients uses daily quick-relief medication, with the belief that it is the most important treatment because of its rapid onset of action; without treating the underlying inflammation. Overuse of short-acting beta2 agonists (SABAs) is associated with increased risk of asthma deaths in a dose-response manner. Beta2 agonists increase the severity of asthma through enhanced bronchial hyperresponsiveness and reduced lung function. Also, it has been shown that overreliance on SABA delays recognition of a potentially life-threatening asthma attack. We believe that overreliance on SABA in asthma is also an important public health issue. The fact that SABA use in GINA is not supported by a randomized trial but by an anonymous paper; makes us guess that we use SABA just because we are used to do so. In 2019 GINA strategy introduces one of the most important changes in the management of Asthma in the past 30 years, highlighting anti-inflammatory reliever therapy. A combination of low dose ICS/fast action bronchodilator will not only treat symptoms, but more importantly the underlying inflammation, protecting patients from preventable asthma attacks. After 50 years of a SABA centric approach in asthma management, it is time to leave behind a treatment based just on the bronchodilation and tackle the inflammation.

Exhaled breath condensate pH in mechanically ventilated patients.

OBJECTIVES: In this prospective clinical trial we aimed to answer if spontaneous exhaled breath condensate (EBC) in the trap of the expiratory arm of the ventilator could replace EBC collected by coolant chamber standardized with Argon as an inert gas. Second, if EBC pH could predict ventilator associated pneumonia (VAP) and mortality. PATIENTS: We included 34 critically ill patients (males = 26), aged = 54.85 ± 19.86 (mean ± SD) yrs, that required mechanical ventilation due to non-pulmonary direct cause (APACHE II score = 23.58 ± 14.7; PaO(2)/FiO(2) = 240.00 ± 98.29). SETTING: ICU with 9 beds from a regional teaching hospital. INTERVENTION AND RESULTS: The patients were followed up until development of VAP, successful weaning or death. There were significant differences between mean EBC pH from the 4 procedures with the exception of spontaneous EBC de-aerated with Argon (n = 79; 6.74 ± 0.28) and coolant chamber deaerated with Argon (n = 79; 6.70 ± 0.36; p = NS by Tukey's Multiple Comparison Test). However, none of the procedures were extrapolated between each other according to Bland & Altman method. The mean EBC pH from the trap without Argon was 6.50 ± 0.28. From the total of 34 patients, 22 survived and were discharged and 12 patients died in the ICU. CONCLUSION: Spontaneous EBC pH could not be extrapolated to EBC pH from coolant chamber and it did not change in subjects who dead, neither subject with VAP in comparison with baseline data. The lack of other biomarker in EBC and the lack of a control group determinate the need for further studies in this setting.

Asthma-related hospitalizations after implementing SABA-free asthma management with a maintenance and anti-inflammatory reliever regimen.

Overreliance on short-acting ß2-agonists (SABA) has been a common feature of asthma management globally for at least 30 years. However, given the evidence against the long-term use of SABA, including potentially increased risk of exacerbations, emergency room visits, overall healthcare resource utilization, and mortality, the latest Global Initiative for Asthma report no longer recommends SABA only therapy. Since 2014, we implemented an ICS-containing reliever strategy at our asthma center at the G Baigorria Hospital in Argentina; we only administered budesonide/formoterol via a single inhaler device across the spectrum of asthma severity and completely eliminated the use of SABA therapy. In this article, we compare hospitalization data from our center, previously reported in the EAGLE study (when inhaled corticosteroids plus as-needed SABA was administered) for the years 1999 and 2004 with data from 2017 to 2018 (when budesonide/formoterol in a single inhaler device was administered as maintenance and/or anti-inflammatory reliever therapy [MART/AIR] without any SABA) from our center, to assess the impact of two distinct asthma management strategies on asthma-related hospitalizations. MART/AIR regimens in our SABA-free center reduced asthma hospitalizations from 9 (1999 and 2004) to 1 (2017 and 2018) (Fisher's exact test, p = 0.031; odds ratio = 0.11; 95% confidence interval [CI] = 0.013-0.98); the hospitalization rate was reduced by 92% (1.47% in 1999 and 2004 to 0.12% in 2017 and 2018). Our data provide preliminary real-world evidence that MART/AIR with budesonide/formoterol simultaneously with SABA elimination across asthma severities is an effective asthma management strategy for reducing asthma-related hospitalizations.

Breath-holding test in subjects with near-fatal asthma. A new index for dyspnea perception.

RATIONALE: Identification of asthmatic subjects with low perception of dyspnea (POD) that are at higher risk of hospitalization, near-fatal and fatal asthma could improve their management. OBJECTIVE: Create a simple procedure that facilitate the recognition of low POD. METHODS: We enrolled near fatal asthma (NFA) subjects and a wide spectrum of non-NFA subjects. Each subject was asked to stop breathing at end-expiration. Dyspnea was assesssed by a modified Borg scale. To design the new index, we combined the Borg score at the end of the voluntary breath-holding maneuver with the airway limitation. The equation was as follows: FEV(1)/FVC%/(breath-holding time in seconds/final Borg score minus basal Borg score). RESULTS: Eleven NFA subjects (4 females) aged 21-73yr and 55 non-NFA (14 severe, 18 moderate and 23 mild asthmatic subjects) completed the study. The threshold value of the index that could predict POD is <12. The mean (+/-sd) of the new index perception was significantly lower in NFA group (n=11; 5.21+/-3.59; vs. n=55; 13.67+/-11.08; P=0.006). This threshold value had 100% sensitivity and it best discriminated between mild and NFA groups. The negative likelihood ratio (when the index > or = 12) was zero. A result > or = 12 represented an almost null probability of poor POD. CONCLUSION: The breath-holding test is simple and rapid. Its negative likelihood ratio was zero. Accordingly, a test result of 12 or greater might exclude the probability of poor perception of dyspnea in subjects with stable asthma.

Combined corticosteroid and long-acting beta-agonist in one inhaler versus inhaled steroids for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have both been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. Their co-administration in a combined inhaler is intended to facilitate adherence to medication regimens, and to improve efficacy. Two preparations are currently available, fluticasone/salmeterol (FPS) and budesonide/formoterol (BDF). OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to inhaled corticosteroids, in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007. SELECTION CRITERIA: Studies were included if they were randomised and double-blind. Studies compared combined inhaled corticosteroids and long-acting beta-agonist preparations with the inhaled corticosteroid component. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The primary outcome were exacerbations, mortality and pneumonia. Health-related quality of life (measured by validated scales), lung function and side-effects were secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios (OR), and continuous data as mean differences and 95% confidence intervals (CI). MAIN RESULTS: Seven studies of good methodological quality met the inclusion criteria randomising 5708 participants with predominantly poorly reversible, severe COPD. Exacerbation rates were significantly reduced with combination therapies (Rate ratio 0.91; 95% confidence interval 0.85 to 0.97, P = 0.0008). Data from two FPS studies indicated that exacerbations requiring oral steroids were reduced with combination therapy. Data from one large study suggest that there is no significant difference in the rate of hospitalisations. Mortality was also lower with combined treatment (odds ratio 0.77; 95% confidence interval 0.63 to 0.94). Quality of life, lung function and withdrawals due to lack of efficacy favoured combination treatment. Adverse event profiles were similar between the two treatments. No significant differences were found between FPS and BDP in the primary outcomes, but the confidence intervals for the BDP results were wide as smaller numbers of patients have been studied. AUTHORS' CONCLUSIONS: Combination ICS and LABA significantly reduces morbidity and mortality in COPD when compared with mono component steroid. Adverse events were not significantly different between treatments, although evidence from other sources indicates that inhaled corticosteroids are associated with increased risk of pneumonia. Assessment of BDF in larger, long-term trials is required. Dose response data would provide valuable evidence on whether efficacy and safety outcomes are affected by different steroid loads.

Combined corticosteroid and long-acting beta-agonist in one inhaler versus long-acting beta-agonists for chronic obstructive pulmonary disease.

BACKGROUND: The co-administration of inhaled corticosteroids and long-acting beta-agonists in a combined inhaler is intended to facilitate adherence to medication regimens, and to improve efficacy in COPD. In this review they are compared with mono component long-acting beta-agonists. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroids and long-acting beta-agonists preparations with mono component long-acting beta-agonists in adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007. SELECTION CRITERIA: Studies were included if they were randomised and double-blind. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with component long-acting beta-agonist preparation. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The primary outcomes were exacerbations, mortality and pneumonia, with health-related quality of life (measured by validated scales), lung function and side-effects as secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios (OR), and continuous data as mean differences and 95% confidence intervals (CI). Sensitivity analysis was performed by combining data with a random effects model. MAIN RESULTS: Ten studies of good methodological quality met the inclusion criteria, randomising 7598 participants with severe chronic obstructive pulmonary disease. Eight studies assessed fluticasone/salmeterol, and two studies budesonide/formoterol. The exacerbation rates with combined inhalers were reduced in comparison to long-acting beta-agonists alone (Rate Ratio 0.82, 95% CI 0.78 to 0.88). There was no significant difference in mortality between combined inhalers and long-acting beta-agonists alone. Pneumonia occurred more commonly with combined inhalers (OR 1.62; 95% CI 1.35 to 1.94). There was no significant difference in terms of hospitalisations, although the two studies contributing data to this outcome may have been drawn from differing populations. Combination was more effective than LABA in improving quality of life measured by the St George Respiratory Questionnaire, and the Chronic Respiratory Questionnaire, and predose and post dose FEV1. AUTHORS' CONCLUSIONS: Combination therapy was more effective than long-acting beta-agonists in reducing exacerbation rates, although the evidence for the effects on hospitalisations was mixed, and requires further exploration. No significant impact on mortality was found even with additional information from the TORCH trial. The superiority of combination inhalers should be viewed against the increased risk of side-effects, particularly pneumonia. Additional studies on BDF are required and more information would be useful of the relative benefits and adverse event rates with different doses of inhaled corticosteroids.

Magnesium sulfate as a vehicle for nebulized salbutamol in acute asthma.

PURPOSE: Magnesium sulfate is thought to be an effective bronchodilator when administered intravenously to patients with acute severe asthma, and it can be safely administered via inhalation to patients with stable asthma. Our goal was to determine if isotonic magnesium sulfate could be used as a vehicle for nebulized salbutamol for patients with acute asthma. METHODS: We enrolled 35 patients with acute asthma in a randomized, double-blind, controlled trial. After measurement of peak expiratory flow, patients received 2.5 mg salbutamol plus either 3 mL normal saline solution (n = 16) or isotonic magnesium sulfate (n = 19) through a jet nebulizer. Peak flow was reassessed 10 and 20 minutes after treatment. RESULTS: Peak flow at baseline was similar in the two groups. Ten minutes after baseline, the mean (+/- SD) percentage increase in peak flow was greater in the magnesium sulfate-salbutamol group (61% +/- 45%) than in the normal saline-salbutamol group (31% +/- 28%; difference = 30%; 95% confidence interval [CI] for the difference: 3% to 56%; P = 0.03). At 20 minutes, the percentage increase in peak flow was 57% greater in the magnesium sulfate group (95% CI: 4% to 110%, P = 0.04). There was a significant inverse correlation between baseline peak flow (percent of predicted) and the percentage increase in peak flow at 20 minutes in the magnesium sulfate group (r = -0.82, P <0.0001), but not in the saline group (r = -0.12, P = 0.67). CONCLUSION: In patients with acute asthma, isotonic magnesium sulfate, as a vehicle for nebulized salbutamol, increased the peak flow response to treatment in comparison with salbutamol plus normal saline.

Effect of inhaled magnesium sulfate on sodium metabisulfite-induced bronchoconstriction in asthma.

BACKGROUND: Inhaled magnesium (Mg) seemed to have a mild protective (nonbronchodilator) effect against histamine and methacholine. Inhaled sodium metabisulfite (MBS) causes bronchoconstriction in asthma through indirect mechanisms that involve sensory nerve stimulation, and it is extensively used to study airway hyperresponsiveness. We designed this double-blind, randomized, crossover, and placebo-controlled study to test the effect of nebulized Mg sulfate against indirect challenge with MBS. METHODS: Ten asthmatic subjects (three male) aged 38.8 (3.29, SEM) years came on three occasions to perform MBS challenges 5 min after inhalation of either normal saline solution as placebo or Mg sulfate (4 mL; 286 mOsm). Doubling increasing concentrations of MBS were administered by continuous nebulization at tidal breathing during 1 min starting at 0.3 to 80 mg/mL until a >20% fall in FEV1 (PC20) from post saline solution baseline value was achieved. PC20 values were logarithmically transformed before analysis. RESULTS: The mean baseline FEV1 at control day was 2.52 (0.14) L and 88.46 (4.28) percentage predicted, while the geometric mean MBS PC20 was 1.95 (1.38, geometric SEM) mg/mL. After placebo, the geometric mean PC20 was 2.26 (1.26) mg/mL. Inhaled Mg increased significantly the PC20 to 5.06 (1.52) mg/mL; p<0.05. Mg diminished the bronchoconstrictor response to MBS by 1.3 doubling doses (p=0.08). CONCLUSIONS: Inhaled Mg attenuates MBS-induced bronchoconstriction in these asthmatic subjects. This new feature of Mg, even modest in magnitude, emphasizes the necessity of studying the potential role of this cation in modulating airway response.

The fatality-prone asthmatic patient. Follow-up study after near-fatal attacks.

We studied 12 fatality-prone patients for 18 months after they had been discharged from the hospital following life-threatening exacerbations of asthma (mean PaCO2 on admission, 97 mm Hg). Our objectives were (1) to evaluate the natural history of their disease during ambulatory care and (2) to investigate whether close follow-up might help to avert further near-fatal events. Only seven of the 12 patients consented to be enrolled in the study, which included monthly scheduled visits to the hospital and monthly telephone calls to record emergency room visits and changes in therapy. By the conclusion of the 18-month follow-up period, two of the noncompliant patients had died during asthmatic attacks. By contrast, all of the seven who had agreed to participate survived; one required intubation and mechanical ventilation, and the other six required occasional unscheduled emergency room visits because of acute exacerbations. Specific precipitants could not be determined, and the most common cause of the acute episodes was likely inadequate steroid therapy. The results suggest that compliance with adequate antiasthmatic therapy and close follow-up may be important in the prevention of near-fatal events.

[Asthma-related mortality in the city of Rosário]. / Mortalidad asociada al asma en el municipio de Rosario.

Accuracy of death certification and registration have been investigated in many countries because death certificates constitute the unavoidable source for studying asthma mortality. The purposes of this study were: 1) to assess the reliability of official registration of asthma death certification and 2) to describe the percentage of asthma deaths occurring outside-hospital in Rosario during 1988. All death certificates from Rosario residents over 5 years old, in which appeared the word asthma or derivatives, were studied. The asthma mortality rates from 1981 to 1989 were obtained from the "Official annual publication". The diagnosis of asthma was written somewhere on 45 certificates; but 30 certificates were interpreted as asthma being the most appropriate diagnosis and could then be coded as the cause of death. These 30 asthma related deaths occurred at the mean age of 59.23 yrs +/- 17.23 (SD), range 12-84 yrs. Twenty-two deaths out of the total of 30 occurred in an out-hospital setting (73%). Among the 30 cases, 8 subjects (aged 63.0 yr +/- 12.38) died in hospital. There was no difference between the age, sex and the death place. Autopsy was performed in only one case of 12 years old. In other 3 cases, asthma was confirmed as the cause of death through the evaluation of case records and the confidential information collected from close acquaintances. The mean asthma mortality rate from 1981 to 88 in Rosario was 5.69 +/- 1.06/10(5), and this value was significantly higher than the death rate calculated by this study (3.46/10(5); p = 0.0005, T test for one sample). The difference probably originated in the false positive certificates often related to procedures in the General Registrar Office. In other words, there was an official overestimation of asthma deaths. This was the first description of the high percentage (73%) of asthma related deaths occurring in the out-hospital setting. Finally, even when death certificates should require a further and exhaustive assessment, asthma mortality rates in Rosario might be regarded as of great concern.

[Effect of ipratropium bromide on histamine-induced bronchoconstriction in subjects with chronic airway obstruction]. / Efecto del bromuro de ipratropio sobre la broncoconstricción por histamina en sujetos con obstrucción crónica al flujo aéreo.

Ipratropium bromide (IB), a quaternary derivative of atropine has been extensively recommended as the first bronchodilator to be tried in chronic obstructive pulmonary disease (COPD). Despite the large information concerning IB use, a controversy still persists about the lack of non bronchodilator effects (preventive) of inhaled IB. Therefore, the purpose was: to study the effects of IB (80 micrograms) on histamine-induced bronchoconstriction in moderate airway obstruction due to COPD. From outpatient clinic 9 men aged (mean +/- SEM) 57.9 +/- 2.4 yr with smoking history of 54.6 +/- 5.1 pack-yrs and a mean FEV1 = 1.36 +/- 0.08 liters (47.2 +/- 3.8% predicted) were enrolled to participate in this randomized placebo-controlled double blind cross-over study. Each subject attended on 3 occasions (first visit was control day; logPC20 = -0.54 +/- 0.24 mg/ml; geometric mean [MG] = 0.27 mg/ml) for histamine challenge tests using the tidal breathing method after either 4 puffs of IB or placebo aerosol. IB significantly increased baseline FEV1. A correlation between baseline obstruction (FEV1; FEV1/FVC) and bronchodilation with airway hyperreactivity (logPC20) could not be demonstrated. The major finding was that IB attenuated the histamine-induced bronchoconstriction (logPC20 = -0.15 +/- 0.17 mg/ml; GM = 0.70 mg/ml) in comparison with placebo (logPC20 = -0.76 +/- 0.22 mg/ml; GM = 0.17 mg/ml; p = 0.018; doubling doses: IB = 2.02 +/- 0.68 vs placebo = -0.62 +/- 0.79; p = 0.024). The lack of correlation between bronchodilator response to IB and the shift in logPC20 might indicate an intrinsic protective role of IB against histamine. Both IB and fenoterol completely resolved the final fall in FEV1 after ending the histamine challenge test. In conclusion, IB diminished histamine-induced bronchoconstriction in these subjects with moderate COPD.

Trends in pharmacotherapy for chronic airflow limitation in Argentina: 1983-1990.

Reported increases in worldwide asthma mortality have prompted the publications of guidelines and consensus statements on the management of airway disease. Overreliance in bronchodilator therapy and lack of anti-inflammatory treatment have been the major findings and the guidelines are aimed at correcting these problems. The Argentinean population appears to have increased prevalence and severity of conditions characterized by chronic airflow limitation and there is no data, to our knowledge, that has analyzed how the treatment of such conditions has been conducted in the past years. Drug sales data in Argentina were surveyed retrospectively to estimate prescriptions dispensed for the treatment of airway disease for the years 1983 to 1990 inclusive. The number of prescriptions of all airway drugs increased significantly (p < 0.01) in the 8-year period except for oral beta 2-agonists and disodium cromoglycate (DSCG). Prescriptions for these agents were 42.7% and 69% less frequent respectively. Thus, oral beta 2-agonists declined from being the single most frequently prescribed class of drugs (40% of prescriptions) in 1983 to the third most frequently prescribed (22%) in 1990. Concurrently, prescriptions of inhaled beta 2-agonists in all forms rose significantly comprising 27% in 1983 and 46% in 1990 becoming the most commonly prescribed airway therapy. Despite this apparent trend away from oral bronchodilator therapy, theophylline prescriptions comprised a significantly higher percentage of prescriptions in 1990 as compared to 1983 (30% vs 20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory arrest in near-fatal asthma.

BACKGROUND AND METHODS: The majority of asthma-related deaths occur outside the hospital, and therefore the exact factors leading to the terminal event are difficult to ascertain. To examine the mechanisms by which patients might die during acute exacerbations of asthma, we studied 10 such patients who arrived at the hospital in respiratory arrest or in whom it developed soon (within 20 minutes) after admission. RESULTS: The characteristics of the group were similar to those associated in the literature with a high risk of death from asthma, including a long history of the disease in young to middle-aged patients, previous life-threatening attacks or hospitalizations, delay in obtaining medical aid, and sudden onset of a rapidly progressive crisis. Extreme hypercapnia (mean [+/- SD] partial pressure of arterial carbon dioxide, 97.1 +/- 31.1 mm Hg) and acidosis (mean [+/- SD] pH, 7.01 +/- 0.11) were found before mechanical ventilation was begun, and four patients had hypokalemia on admission. Despite the severe respiratory acidosis, no patient had a serious cardiac arrhythmia during the resuscitation maneuvers or during hospitalization. We observed systemic hypertension and sinus tachycardia in eight patients, atrial fibrillation in one, and sinus bradycardia in another. In both patients with arrhythmia the heart reverted to sinus rhythm immediately after manual ventilation with 100 percent oxygen was begun. The median duration of mechanical ventilation was 12 hours, and all patients had normocapnia on discharge from the hospital. CONCLUSIONS: We conclude that at least in this group of patients, the near-fatal nature of the exacerbations was the result of severe asphyxia rather than cardiac arrhythmias. These results suggest that undertreatment rather than overtreatment may contribute to an increase in mortality from asthma.

Effect of inhaled furosemide in acute asthma.

We assessed the acute bronchodilator effect of nebulized furosemide when added to conventional therapy of acute emergency department (ED) asthma. Using a double-blind design, 42 patients with acute asthma were randomized to receive 2.5 mg nebulized salbutamol and either 40 mg of nebulized furosemide or saline solution. We recorded clinical variables (respiratory rate, heart rate, and pulsus paradoxus) and peak expiratory flow rates (PEFR) before and 15 and 30 min after therapy. We found no significant difference in PEFR between salbutamol/furosemide and salbutamol/saline-treated patients 15 and 30 min following inhalation. Other endpoints were equally unaffected. However, when we examined separately those patients whose exacerbations were of relative short duration (< 8 hr), PEFR improved significantly more in the furosemide-treated group. At 15 min, PEFR increased by 82 +/- 48% in the furosemide group compared to 35 +/- 40% in the control group (p = 0.03), an effect that was also evident at 30 min when PEFR had increased by 113 +/- 49% in the furosemide group versus 61 +/- 35% in the control group (p = 0.014). Respiratory rate, heart rate, and pulsus paradoxus improved with no differences between the groups. The beneficial effect of furosemide was not evident in patients who reported more prolonged duration (> 8 hr) of asthmatic symptoms. The response to furosemide appeared to be unrelated to concomitant ED therapy with corticosteroids, to baseline pulmonary function, or to patient demographic variables. We conclude that furosemide may offer additive bronchodilator benefits in acute naturally occurring asthma of relative short duration.

Efecto del bromuro de ipratropio sobre la broncoconstricción por histamina en sujetos con obstrucción crónica al flujo aéreo. / [Effect of ipratropium bromide on histamine-induced bronchoconstriction in subjects with chronic airway obstruction]

Ipratropium bromide (IB), a quaternary derivative of atropine has been extensively recommended as the first bronchodilator to be tried in chronic obstructive pulmonary disease (COPD). Despite the large information concerning IB use, a controversy still persists about the lack of non bronchodilator effects (preventive) of inhaled IB. Therefore, the purpose was: to study the effects of IB (80 micrograms) on histamine-induced bronchoconstriction in moderate airway obstruction due to COPD. From outpatient clinic 9 men aged (mean +/- SEM) 57.9 +/- 2.4 yr with smoking history of 54.6 +/- 5.1 pack-yrs and a mean FEV1 = 1.36 +/- 0.08 liters (47.2 +/- 3.8

predicted) were enrolled to participate in this randomized placebo-controlled double blind cross-over study. Each subject attended on 3 occasions (first visit was control day; logPC20 = -0.54 +/- 0.24 mg/ml; geometric mean [MG] = 0.27 mg/ml) for histamine challenge tests using the tidal breathing method after either 4 puffs of IB or placebo aerosol. IB significantly increased baseline FEV1. A correlation between baseline obstruction (FEV1; FEV1/FVC) and bronchodilation with airway hyperreactivity (logPC20) could not be demonstrated. The major finding was that IB attenuated the histamine-induced bronchoconstriction (logPC20 = -0.15 +/- 0.17 mg/ml; GM = 0.70 mg/ml) in comparison with placebo (logPC20 = -0.76 +/- 0.22 mg/ml; GM = 0.17 mg/ml; p = 0.018; doubling doses: IB = 2.02 +/- 0.68 vs placebo = -0.62 +/- 0.79; p = 0.024). The lack of correlation between bronchodilator response to IB and the shift in logPC20 might indicate an intrinsic protective role of IB against histamine. Both IB and fenoterol completely resolved the final fall in FEV1 after ending the histamine challenge test. In conclusion, IB diminished histamine-induced bronchoconstriction in these subjects with moderate COPD.

Mortalidad asociada al asma en el municipio de Rosario. / [Asthma-related mortality in the city of Rosário]

Accuracy of death certification and registration have been investigated in many countries because death certificates constitute the unavoidable source for studying asthma mortality. The purposes of this study were: 1) to assess the reliability of official registration of asthma death certification and 2) to describe the percentage of asthma deaths occurring outside-hospital in Rosario during 1988. All death certificates from Rosario residents over 5 years old, in which appeared the word asthma or derivatives, were studied. The asthma mortality rates from 1981 to 1989 were obtained from the [quot ]Official annual publication[quot ]. The diagnosis of asthma was written somewhere on 45 certificates; but 30 certificates were interpreted as asthma being the most appropriate diagnosis and could then be coded as the cause of death. These 30 asthma related deaths occurred at the mean age of 59.23 yrs +/- 17.23 (SD), range 12-84 yrs. Twenty-two deaths out of the total of 30 occurred in an out-hospital setting (73

). Among the 30 cases, 8 subjects (aged 63.0 yr +/- 12.38) died in hospital. There was no difference between the age, sex and the death place. Autopsy was performed in only one case of 12 years old. In other 3 cases, asthma was confirmed as the cause of death through the evaluation of case records and the confidential information collected from close acquaintances. The mean asthma mortality rate from 1981 to 88 in Rosario was 5.69 +/- 1.06/10(5), and this value was significantly higher than the death rate calculated by this study (3.46/10(5); p = 0.0005, T test for one sample). The difference probably originated in the false positive certificates often related to procedures in the General Registrar Office. In other words, there was an official overestimation of asthma deaths. This was the first description of the high percentage (73

) of asthma related deaths occurring in the out-hospital setting. Finally, even when death certificates should require a further and exhaustive assessment, asthma mortality rates in Rosario might be regarded as of great concern.

Trends in pharmacotherapy for chronic airflow limitation in Argentina: 1983-1990.

Reported increases in worldwide asthma mortality have prompted the publications of guidelines and consensus statements on the management of airway disease. Overreliance in bronchodilator therapy and lack of anti-inflammatory treatment have been the major findings and the guidelines are aimed at correcting these problems. The Argentinean population appears to have increased prevalence and severity of conditions characterized by chronic airflow limitation and there is no data, to our knowledge, that has analyzed how the treatment of such conditions has been conducted in the past years. Drug sales data in Argentina were surveyed retrospectively to estimate prescriptions dispensed for the treatment of airway disease for the years 1983 to 1990 inclusive. The number of prescriptions of all airway drugs increased significantly (p < 0.01) in the 8-year period except for oral beta 2-agonists and disodium cromoglycate (DSCG). Prescriptions for these agents were 42.7

and 69

less frequent respectively. Thus, oral beta 2-agonists declined from being the single most frequently prescribed class of drugs (40

of prescriptions) in 1983 to the third most frequently prescribed (22

) in 1990. Concurrently, prescriptions of inhaled beta 2-agonists in all forms rose significantly comprising 27

in 1983 and 46

in 1990 becoming the most commonly prescribed airway therapy. Despite this apparent trend away from oral bronchodilator therapy, theophylline prescriptions comprised a significantly higher percentage of prescriptions in 1990 as compared to 1983 (30

vs 20

).(ABSTRACT TRUNCATED AT 250 WORDS)