Carlos Cezar Fritscher

Asthma control in Latin America: the Asthma Insights and Reality in Latin America (AIRLA) survey

OBJECTIVES The aims of this survey were (1) to assess the quality of asthma treatment and control in Latin America, (2) to determine how closely asthma management guidelines are being followed, and (3) to assess perception, knowledge and attitudes related to asthma in Latin America. METHODS We surveyed a household sample of 2,184 adults or parents of children with asthma in 2003 in 11 countries in Latin America. Respondents were asked about healthcare utilization, symptom severity, activity limitations and medication use. RESULTS Daytime asthma symptoms were reported by 56% of the respondents, and 51% reported being awakened by their asthma at night. More than half of those surveyed had been hospitalized, attended a hospital emergency service or made unscheduled emergency visits to other healthcare facilities for asthma during the previous year. Patient perception of asthma control did not match symptom severity, even in patients with severe persistent asthma, 44.7% of whom regarded their disease as being well or completely controlled. Only 2.4% (2.3% adults and 2.6% children) met all criteria for asthma control. Although 37% reported treatment with prescription medications, only 6% were using inhaled corticosteroids. Most adults (79%) and children (68%) in this survey reported that asthma symptoms limited their activities. Absence from school and work was reported by 58% of the children and 31% of adults, respectively. CONCLUSIONS Asthma control in Latin America falls short of goals in international guidelines, and in many aspects asthma care and control in Latin America suffer from the same shortcomings as in other areas of the world.

Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study

BACKGROUND We compared the efficacy and safety of indacaterol and tiotropium in patients with severe chronic obstructive pulmonary disease (COPD) and a history of at least one moderate to severe exacerbation in the previous 12 months. METHODS In this multicentre, randomised, blinded, double-dummy, parallel group study, we enrolled patients aged 40 years or older with severe COPD and at least one exacerbation within the previous year. We used a computer-generated sequence to randomly allocate patients (1:1; stratified by baseline inhaled corticosteroid use, with the balance of treatments maintained at country level) to receive either indacaterol (150 μg) or tiotropium (18 μg) once-daily for 52 weeks. Our primary and key secondary objectives were to investigate whether indacaterol was non-inferior to tiotropium for trough forced expiratory volume in 1 s (FEV1) at week 12 (primary endpoint), and for rate of exacerbations at week 52 (secondary endpoint). Analysis populations for the primary and key secondary endpoints were per-protocol sets. The safety set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00845728. FINDINGS Between March 16, 2009, and July 5, 2012, we enrolled and randomly allocated 3444 patients: 1723 to indacaterol and 1721 to tiotropium. At week 12, the estimated least squares mean trough FEV1 difference between the groups was -0.011 L (least squares mean with indacaterol [n=1450] 1.134 L [SE 0.008] vs tiotropium [n=1467] 1.145 L [0.008]; one-sided 97.5% CI lower limit -0.026 L; p<0.0001). The lower limit of the 97.5% CI was above the prespecified non-inferiority margin of -0.055 L, suggesting that indacaterol was non-inferior to tiotropium. Indacaterol did not show non-inferiority in terms of annualised exacerbation rates: 0.79 (indacaterol, n=1529) versus 0.61 (tiotropium, n=1543); ratio 1.29 (one-sided 97.5% CI upper limit 1.44). In the safety set, we recorded no between-group difference in the number of patients who had adverse events (indacaterol 1119 [65%] of 1721 patients vs tiotropium 1065 [62%] of 1718 patients) or serious adverse events (indacaterol, 263 [15%] of 1721 patients vs tiotropium, 255 [15%] of 1718 patients). Respiratory disorders, particularly worsening of COPD, were the most common adverse events (COPD: indacaterol, 747 [43%] of 1721 patients and tiotropium, 665 [39%] of 1718 patients) and serious adverse events (COPD: indacaterol, 147 [9%] of 1721 patients and tiotropium, 121 [7%] of 1718 patients). INTERPRETATION Indacaterol and tiotropium provided clinically relevant improvements in lung function with comparable safety profiles. Tiotropium afforded greater protection from exacerbations, although the absolute number of events was small and the difference between treatments is of uncertain clinical importance. The present data offer evidence consistent with current guidelines. FUNDING Novartis Pharma AG.

Adesão ao tratamento de manutenção em asma (estudo ADERE)

OBJECTIVE To determine the rate of compliance with preventive treatment of moderate and severe persistent asthma. METHODS Physicians at various medical centers across the country were invited to nominate patients for participation in the study. Inclusion criteria were being over the age of 12 and presenting moderate or severe persistent asthma. Participating patients received salmeterol/fluticasone 50/250 microg by dry powder inhaler for 90 days and were instructed to return the empty packages at the end of the study as a means of determining the total quantity used. In order to evaluate compliance, a member of the research team contacted each patient via telephone at the study outset and again at the end of the 90-day study period. Asthma patients were considered compliant with the treatment if they used at least 85% of the prescribed dose. The following variables were studied: gender, age, race, marital status, years of schooling, smoking habits, other atopic conditions, comorbidities, asthma severity, use of other medication and number of hospital admissions for asthma. RESULTS A total of 131 patients from fifteen states were included. The overall rate of compliance was found to be 51.9%. There was a significant difference in compliance in relation to asthma severity: compliance was greater among patients with severe persistent asthma than among those with moderate persistent asthma (p = 0.02). There were no statistically significant differences among any of the other variables. CONCLUSION The overall rate of compliance with maintenance treatment of asthma was low.

Variação na prevalência de asma e atopia em um grupo de escolares de Porto Alegre, Rio Grande do Sul

Introduction: A considerable increase in asthma and atopy prevalence has been noticed worldwide through the last decades, however, in our country, epidemiological data are still insufficient. Objective: This study was carried out to determine the prevalence of asthma and atopy in a group of students, and compare these data with those found in two previous studies undertaken in Porto Alegre, Rio Grande do Sul. Methods: Asthma prevalence was identified through a questionnaire applied to 855 students from five schools of Porto Alegre. The students submitted to skin tests who presented, at least, one positive reaction were considered atopic. The signature of an informed consent from one of the parents was required for the skin test performance. Results: Prevalence was found to be 42.5% and 22% of cumulative and active asthma, respectively, with predominance in females. Atopy was identified in 50.1% of the sample. These results were significantly higher than the 6.7% (1980) and 16% (1989) of cumulative asthma, 10.9% (1989) of active asthma and 15.8% (1980) of atopy found in the two previous studies. Conclusion: A high prevalence of asthma and atopy was identified in our students. Future studies should be performed to elucidate the phenomenon herein demonstrated.

Impact of a Low-Cost and Simple Intervention in Enhancing Treatment Adherence in a Brazilian Asthma Sample

The aim of this study was to evaluate adherence to treatment in persistent asthma in Brazil to determine the factors associated with non-adherence and to measure the efficacy of telephone calls in enhancing adherence. In a prospective, multicenter, interventional clinical trial with parallel groups, asthmatics were randomized into an intervention group or a control group. Asthmatics included in the intervention group received an initial telephone call to record demographic information and asthma characterization. After that, biweekly telephone calls were made to promote treatment adherence. Asthmatics included in the control group received only the initial and final telephone calls. Both groups received three packages of salmeterol/fluticasone for 3 months. The main outcome measure was the percentage of participants who took the prescribed doses of the drug. A total of 271 patients were included. The overall adherence rate was 51.9% for the control group and 74.3% for the intervention group. This meant a reduction of relative risk (RRR) of 47% (p < 0.001). The number needed to treat (NNT) was 4.5. The only variable associated with better adherence was severe persistent asthma. A low-cost easily implemented intervention, tailored to each individual, enhanced the adherence rate among Brazilian asthmatic patients.

Is there a gender difference in non-small cell lung cancer survival?

BACKGROUND A possible association had previously been noted between gender and prognosis in non-small cell lung cancer (NSCLC), with a better survival rate for women. OBJECTIVE The purpose of the current study was to further clarify the role of gender as a possible prognostic factor in NSCLC. METHODS This retrospective cohort study examined the survival of NSCLC patients who underwent surgical curative treatment at the Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil, between January 1, 1990, and December 31, 2000. Data were analyzed using Kaplan-Meier survival curves. In addition, a Cox proportional hazards regression model was used to adjust for potential confounding factors. RESULTS In the period studied, lung resections were performed in 253 patients with NSCLC, of whom 114 had stage I tumors. Four patients were excluded because of death in the immediate postoperative period, and 1 committed suicide. The 5-year survival rate was 85.5% for women and 46.4% for men (P<0.0001). The median overall survival time was 44.7 months (interquartile range [IQR(25%-75%)], 17.4-72.3 months) and was longer in women than in men: 63.9 months (IQR(25%5%), 35.2-98.7 months) versus 32.3 months (IQR(25%-75%), 11.8-61.5 months), respectively (P<0.0001). Gender effect was still present after adjustment by Cox regression for several factors (age, smoking habits, hemoglobin, forced expiratory volume in 1 second, tumor size, tumor-node-metastasis stage, histology, postoperative complications, and surgery type). The adjusted hazard ratio in women was 0.23 (95% CI, 0.09-0.59; (P<0.0001) when compared with men. CONCLUSION This study confirms previous findings that women live longer than men after surgery for stage I NSCLC. This effect persisted after adjusting for several factors. These results highlight the fact that analyses of long-term survival of NSCLC patients, usually generalized to men and women as a whole, may be an inadequate extrapolation. These results question whether analyses of long-term survival, which commonly group men and women together, provide an adequate prognosis of survival rates in women with NSCLC.

Nontuberculous Mycobacterial Infection as a Cause of Difficult-to-Control Asthma: A Case-Control Study

BACKGROUND Symptomatic disease due to nontuberculous mycobacteria (NTM) is known to occur commonly in the presence of structural lung disease, but is not described in association with asthma. METHODS This was a case-control study nested in a cohort. We identified 22 patients with difficult asthma referred to a tertiary academic referral center and subsequently found to have infection with NTM. We matched each case with two control subjects (next two consecutive patients referred for asthma management). RESULTS It took on average 2.1 years from the onset of new or worsening symptoms to NTM diagnosis. The most common symptoms were worsening cough (77%), sputum production (40.9%), and frequent exacerbations (31.8%). Mycobacterium avium complex accounted for 63.6% of the infections, Mycobacterium xenopi the balance. Case subjects were older (59.8 ± 8.9 vs 42.6 ± 18 years; P < .001) and had more severe airflow obstruction (FEV(1), 57% [40%-74%] vs 89.5% [80%-98%]; P < .001). There was no difference between case and control subjects in the proportion using inhaled corticosteroids (ICS) or the average daily dose at the time of presentation, but case subjects had used ICS for a longer period (17 [6.2-20] vs 4 [0.75-6.0] years; P=.002). Six subjects with NTM were being treated with daily oral steroids, whereas none of the control subjects was. Of the 22 cases, 10 were treated with antibiotics for NTM, seven demonstrating clinical improvement or resolution of the presenting symptoms. CONCLUSIONS NTM infection can be associated with asthma and should be considered in difficult-to-treat disease, especially in older individuals with more severe airflow obstruction and greater exposure to inhaled or systemic corticosteroids.

O papel do aleitamento materno, da dieta e do estado nutricional no desenvolvimento de asma e atopia

In many populations, the prevalence of asthma and atopy has increased in recent years. As a result, both conditions have become major public health problems. The possible influence of nutrition-related factors has been demonstrated in an increasing number of studies. Information regarding the role of breastfeeding, diet, nutritional status (obesity in particular), as well as regarding the immunologic responses triggered, helps to improve our understanding of the correlation between oxidative stress, bronchial inflammation, and the development of atopic and asthma symptoms. The article presents a review of the published literature on the relationships established between and among nutrition, asthma, and atopy over the last two decades.

The influence of poor nutrition on the necessity of mechanical ventilation among children admitted to the Pediatric Intensive Care Unit

OBJECTIVE To determine the relation between childrens nutritional status when they are admitted to the Pediatric Intensive Care Unit, the necessity and length of mechanical ventilation and the mortality rate. METHODS A cohort study was conducted between July 1st, 1995 and June 30th, 1996. This study involved all children (28 days old to 48 months old) admitted to the pediatric intensive care unit of Hospital São Lucas, who stayed there longer than 8 hours. Exclusion criteria were complex cardiac disease, admission to the pediatric intensive care unit for elective procedure (regardless of pediatric intensive care unit admission criteria) or elective mechanical ventilation (cardiac, thoracic or other postoperative period). The staff responsible for the daily data collection were not involved with patient care or assistance decisions. On the day of admission to the pediatric intensive care unit, patients were evaluated regarding their nutritional status through the z score and the severity of the disease using the Pediatric Risk Mortality score. Demographic data, necessity and length of mechanical ventilation as well as main diagnosis and evolution of each patient were evaluated every day. RESULTS Malnourishment increased significantly the need for mechanical ventilation, especially when associated with (a) age under one year old (RR=2.4; 1.4-3.8); (b) children admitted to the pediatric intensive care unit with low Pediatric Risk Mortality score (less than 10) (RR=2.5; 1.3-4.7); (c) presence of respiratory disease (RR=2.1; 1.3-4.7). Otherwise, malnourishment did not show any influence on the mortality rate. CONCLUSION In our study, we could demonstrate that malnourishment in children under 4 years old admitted to the pediatric intensive care unit represented a decisive factor on evolution, increasing significantly the necessity and the length of mechanical ventilation as well as the length of stay at the pediatric intensive care unit.

Asthma Mortality in Southern Brazil: Is There a Changing Trend?

Background. Mortality from asthma increased during the last decades but is now declining in some countries. Little is known about this trend in Brazil. Objective. The objective of the study was to determine the trends in asthma mortality in Southern Brazil. Methods. We reviewed death certificates of 566 people in the state of Rio Grande do Sul, Brazil, between 5 and 39 years of age in whom asthma was reported to be the underlying cause of death during the period of 1981-2003. Population data were available in 5-year age groups. Mortality rates were submitted to linear and quadratic regression procedures. Results. Among children and teenagers (5–19 years), there were 170 asthma deaths, ranging from 4 to 13 deaths each year with rates of 0.154/100,000 to 0.481/100,000. In young adults (20–39 years), 396 asthma deaths occurred, ranging from 9 to 32 each year, with rates from 0.276/100,000 to 1.034/100,000. There was an initial increase in rates, with later stabilization, and then the start of a decline beginning in the late 1990s and the early part of this decade. This trend occurred in both age subgroups examined but was more evident in males. Conclusions. Asthma mortality in southern Brazil remains low and appears to be decreasing after reaching a peak in the mid-1990s. The reason for these trends remains unknown.