Polysomnographic evaluation of obstructive sleep apnea treatment with fixed pressure CPAP determined by formula.

PURPOSE: The use of continuous positive airway pressure (CPAP) is one of the therapeutic modalities for obstructive sleep apnea (OSA). Manual titration polysomnography and the 90th or 95th percentiles of pressure titrated by automatic CPAP (APAP) are the current standard for determining fixed pressure. Pressures programmed at an arbitrary fixed value, or at preset values based on body mass index (BMI) or by predictive formulas, are presented as alternative forms. This study aimed to evaluate the residual apnea-hypopnea index (r-AHI) in polysomnography with CPAP therapy using pressure determined by formula and assess its feasibility to start treatment. METHODS: Patients referred for CPAP therapy were followed up in three outpatient assessments and underwent polysomnography study with pressure CPAP obtained by formula. RESULTS: The study sample consisted of 80 patients, 41 women; age 58.6 ± 11.3 years, BMI 34.1 ± 7.5 kg/m2 and cervical circumference 42.0 ± 4.2 cm. Most patients (74%) had severe OSA and Epworth sleepiness scale (ESS) of 12.0 ± 5.7 points. The calculated average pressure was 7.8 ± 2.1 cmH2O. Polysomnography studies showed an r-AHI of 6.1 ± 5.2 events/h and reduction of 84% from baseline AHI. The r-AHI in the REM-supine was 8.4 ± 9.9 events/h. At 30- and 120-day follow-up assessment, adherence to CPAP was 78% and 75% and the ESS score was 6.9 and 6.1 points, respectively. CONCLUSION: Results suggest that a formula provides an effective initial pressure in the majority of patients (73%). This simplified approach appears to be a viable alternative, with reductions in waiting lists and time from diagnosis to initiation of therapy.

The efficacy and safety of mannitol challenge in a workplace setting for assessing asthma prevalence.

OBJECTIVE: There is no standard definition of asthma for epidemiological purposes; most surveys use symptoms and bronchial hyperresponsiveness. Few studies tested mannitol challenge test (MCT) in occupational settings. We sought to determine efficacy and safety of MCT in detecting subjects with asthma symptoms in the workplace. METHODS: In this cross-sectional study we recruited 908 workers in 2 universities; they underwent a respiratory questionnaire, spirometry, skin prick tests, and MCT. RESULTS: Eight hundred and eleven subjects completed the study; 11.1% had a positive MCT; 8.14% had asthma. MCT had low sensitivity (35.4-61.9%) but high specificity (90.2-94.9%) to detect symptomatic individuals. The most prevalent symptom was wheezing in the last 12 months. Twenty-four of those with a positive MCT (26.7%) had no positive replies to the questions on asthma symptoms. Among subjects with a positive MCT, 71.9% achieved 95% of baseline FEV1 after 15 minutes of salbutamol recovery treatment. Nine subjects (1.1%) had adverse events that prevented the test from being completed. CONCLUSIONS: MCT has high specificity but low sensitivity to detect symptomatic subjects in the workplace. It may detect subjects with hyperresponsiveness but no symptoms, who could be at risk of developing airway diseases. The test is safe and well tolerated.

Oral administration of Saccharomyces cerevisiae UFMG A-905 prevents allergic asthma in mice.

BACKGROUND AND OBJECTIVE: The prevalence of asthma has increased in communities that adopt a Western lifestyle and become more urbanized. Probiotics may be effective in the prevention of allergic diseases, such as asthma. The aim of the current study was to examine the effects of Saccharomyces cerevisiae UFMG A-905 in an allergic model of asthma. METHODS: Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally, 1 week apart and challenged with OVA intranasally for 3 days. Mice were daily treated with S. cerevisiae UFMG A-905 via gavaging needle 10 days before OVA sensitization and during challenges. After challenge, in vivo lung function was measured, and bronchoalveolar lavage (BAL) and lung inflammation were assessed. RESULTS: Oral treatment with S. cerevisiae UFMG A-905 significantly decreased airway hyperresponsiveness, total cell number and the influx of eosinophils to the airway, inflammatory cell in the lung, mucus expression in epithelial cells and the levels of IL-4, IL-5 and IL-13. Additionally, S. cerevisiae UFMG A-905 restored the levels of IL-10 and interferon (IFN)-gamma, and increased the levels of IL-17A. CONCLUSION: Oral administration of S. cerevisiae UFMG A-905 prevented the development of major asthma-like characteristics in a mouse model.

Prevalence of non-communicable diseases in Brazilian children: follow-up at school age of two Brazilian birth cohorts of the 1990's.

BACKGROUND: Few cohort studies have been conducted in low and middle-income countries to investigate non-communicable diseases among school-aged children. This article aims to describe the methodology of two birth cohorts, started in 1994 in Ribeirão Preto (RP), a more developed city, and in 1997/98 in São Luís (SL), a less developed town. METHODS: Prevalences of some non-communicable diseases during the first follow-up of these cohorts were estimated and compared. Data on singleton live births were obtained at birth (2858 in RP and 2443 in SL). The follow-up at school age was conducted in RP in 2004/05, when the children were 9-11 years old and in SL in 2005/06, when the children were 7-9 years old. Follow-up rates were 68.7% in RP (790 included) and 72.7% in SL (673 participants). The groups of low (<2500 g) and high (≥ 4250 g) birthweight were oversampled and estimates were corrected by weighting. RESULTS: In the more developed city there was a higher percentage of non-nutritive sucking habits (69.1% vs 47.9%), lifetime bottle use (89.6% vs 68.3%), higher prevalence of primary headache in the last 15 days (27.9% vs 13.0%), higher positive skin tests for allergens (44.3% vs 25.3%) and higher prevalence of overweight (18.2% vs 3.6%), obesity (9.5% vs 1.8%) and hypertension (10.9% vs 4.6%). In the less developed city there was a larger percentage of children with below average cognitive function (28.9% vs 12.2%), mental health problems (47.4% vs 38.4%), depression (21.6% vs 6.0%) and underweight (5.8% vs 3.6%). There was no difference in the prevalence of bruxism, recurrent abdominal pain, asthma and bronchial hyperresponsiveness between cities. CONCLUSIONS: Some non-communicable diseases were highly prevalent, especially in the more developed city. Some high rates suggest that the burden of non-communicable diseases will be high in the future, especially mental health problems.

Insulin modulates cytokine release and selectin expression in the early phase of allergic airway inflammation in diabetic rats.

BACKGROUND: Clinical and experimental data suggest that the inflammatory response is impaired in diabetics and can be modulated by insulin. The present study was undertaken to investigate the role of insulin on the early phase of allergic airway inflammation. METHODS: Diabetic male Wistar rats (alloxan, 42 mg/Kg, i.v., 10 days) and controls were sensitized by s.c. injection of ovalbumin (OA) in aluminium hydroxide 14 days before OA (1 mg/0.4 mL) or saline intratracheal challenge. The following analyses were performed 6 hours thereafter: a) quantification of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC)-1 in the bronchoalveolar lavage fluid (BALF) by Enzyme-Linked Immunosorbent Assay, b) expression of E- and P- selectins on lung vessels by immunohistochemistry, and c) inflammatory cell infiltration into the airways and lung parenchyma. NPH insulin (4 IU, s.c.) was given i.v. 2 hours before antigen challenge. RESULTS: Diabetic rats exhibited significant reduction in the BALF concentrations of IL-1beta (30%) and TNF-alpha (45%), and in the lung expression of P-selectin (30%) compared to non-diabetic animals. This was accompanied by reduced number of neutrophils into the airways and around bronchi and blood vessels. There were no differences in the CINC-1 levels in BALF, and E-selectin expression. Treatment of diabetic rats with NPH insulin, 2 hours before antigen challenge, restored the reduced levels of IL-1beta, TNF-alpha and P-selectin, and neutrophil migration. CONCLUSION: Data presented suggest that insulin modulates the production/release of TNF-alpha and IL-1beta, the expression of P- and E-selectin, and the associated neutrophil migration into the lungs during the early phase of the allergic inflammatory reaction.

Influence of nocturnal asthma on chronotype.

Individual differences in circadian rhythm have been studied since the past century. Chronotypes are a chronobiology classification based on the preferential times for beginning and ending activities throughout the day. Chronotypes can be classified as definitely morning, moderately morning, indifferent, moderately evening, and definitely evening. We aim to assess the distribution of chronotypes in asthmatics and the relationship of chronotype to the presence of nocturnal symptoms. Two hundred subjects were evaluated, 100 asthmatics and 100 non-asthmatics. The Morningness/Eveningness questionnaire was applied for chronotype determination. The asthmatics were subdivided according to the presence or absence of nocturnal symptoms. The chronotype distribution did not differ significantly between asthmatics and non-asthmatics. Thirty-five percent of the asthma group reported nocturnal symptoms. There was a significant difference in chronotype distribution between asthmatics with and without nocturnal worsening. The asthmatics with nocturnal symptoms had a lower prevalence of morning types and had a greater predominance of indifferent chronotype compared to asthmatics without nocturnal symptoms (p = 0.011). In conclusion, asthmatics with nocturnal symptoms present deviation from the chronotype distribution curve when compared to asthmatics without nocturnal symptoms. This is the first study to show the effect of a disease on chronotypes.

Lung function and airway hyperresponsiveness in adult patients with sickle cell disease.

BACKGROUND: Lung disease is a major cause of morbidity and death in sickle cell disease. Although airway hyperresponsiveness has been noted in children, there are no studies in adult sickle cell patients. The aim of this study was to investigate the prevalence of airway hyperresponsiveness in adult sickle cell patients. METHODS: Twenty-six patients with sickle cell disease (10 HbSC, 9 HbSS, and 7 HbSbeta) were compared with 28 normal control subjects. Pulmonary function tests, including spirometry, measurements of single-breath diffusing capacity and the methacholine challenge test were performed. RESULTS: There were no significant differences in age, gender, or height between groups. Restrictive ventilatory defect was observed in six patients (24%) in the sickle cell disease group. Obstructive ventilatory defect and reduced diffusing lung DLCO capacity was observed in all sickle cell disease subgroups. A positive methacholine challenge test was obtained in eight (31%) sickle cell patients and in two of the 28 controls (7%). CONCLUSION: These features suggest that there is a high prevalence of airway hyperresponsiveness in adult patients with sickle cell disease without a history of reactive airway disease.

Laboratory animals and respiratory allergies: the prevalence of allergies among laboratory animal workers and the need for prophylaxis.

OBJECTIVE: Subjects exposed to laboratory animals are at a heightened risk of developing respiratory and allergic diseases. These diseases can be prevented by simple measures such as the use of personal protective equipment. We report here the primary findings of the Laboratory Animals and Respiratory Allergies Study regarding the prevalence of allergic diseases among laboratory animal workers, the routine use of preventive measures in laboratories and animal facilities, and the need for prevention programs. METHODS: Animal handlers and non-animal handlers from 2 Brazilian universities (University of São Paulo and State University of Campinas) answered specific questionnaires to assess work conditions and symptoms. These subjects also underwent spirometry, a bronchial challenge test with mannitol, and skin prick tests for 11 common allergens and 5 occupational allergens (rat, mouse, guinea pig, hamster, and rabbit). RESULTS: Four hundred fifty-five animal handlers (32±10 years old [mean±SD], 209 men) and 387 non-animal handlers (33±11 years old, 121 men) were evaluated. Sensitization to occupational allergens was higher among animal handlers (16%) than non-animal handlers (3%, p<0.01). Accessibility to personal protective equipment was measured at 85% (median, considering 73 workplaces of the animal handler group). Nineteen percent of the animal handlers indicated that they wear a respirator at all times while handling animals or working in the animal room, and only 25% of the animal handlers had received an orientation about animal-induced allergies, asthma, or rhinitis. CONCLUSION: In conclusion, our data indicate that preventive programs are necessary. We suggest providing individual advice to workers associated with institutional programs to promote a safer work environment.

Cough and dyspnea during bronchoconstriction: comparison of different stimuli.

BACKGROUND: Bronchial challenge tests are used to evaluate bronchial responsiveness in diagnosis and follow-up of asthmatic patients. Challenge induced cough has increasingly been recognized as a valuable diagnostic tool. Various stimuli and protocols have been employed. The aim of this study was to compare cough and dyspnea intensity induced by different stimuli. METHODS: Twenty asthmatic patients underwent challenge tests with methacholine, bradykinin and exercise. Cough was counted during challenge tests. Dyspnea was assessed by modified Borg scale and visual analogue scale. Statistical comparisons were performed by linear mixed-effects model. RESULTS: For cough evaluation, bradykinin was the most potent trigger (p < 0.01). In terms of dyspnea measured by Borg scale, there were no differences among stimuli (p > 0.05). By visual analogue scale, bradykinin induced more dyspnea than other stimuli (p < or = 0.04). CONCLUSION: Bradykinin seems to be the most suitable stimulus for bronchial challenge tests intended for measuring cough in association with bronchoconstriction.

Bronchial responsiveness during esophageal acid infusion.

Among the possible mechanisms explaining the worsening of asthma due to gastroesophageal reflux disease (GERD) is the increase in bronchial hyperresponsiveness. The effects of GERD on bronchial hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The aim of this study was to determine the effects of esophageal acid perfusion on bronchial responsiveness to bradykinin in patients with both asthma and GERD. In 20 patients with asthma and GERD disease, esophageal pH was monitored with a pH meter and bronchial responsiveness was evaluated by aerosol inhalation of bradykinin during esophageal acid perfusion and, 24 h earlier or later the patients were submitted to another bronchial provocation test without acid infusion. No significant changes were observed in FEV(1), FEF(25-75%), FVC, or PEF during acid perfusion. The response to the bronchial provocation test did not differ between the control day and the day of acid infusion (p = 0.61). The concentration provoking a 20% fall in FEV(1) (geometric mean +/- geometric SD) was 1.09 +/- 5.84 on the day of acid infusion and 0.98 +/- 5.52 on the control day. There is no evidence that acid infusion changes bronchial responsiveness to bradykinin. These findings strongly question the significance of acid infusion as a model to study the pathogenesis of GERD-induced asthma.

Inflammatory and functional effects of increasing asthma treatment with formoterol or double dose budesonide.

Adding a long-acting beta(2)-agonist to inhaled corticosteroids (ICS) for asthma treatment is better than increasing ICS dose in improving clinical status, although there is no consensus about the impact of this regimen on inflammation. In this double-blind, randomized, parallel group study, asthmatics with moderate to severe disease used budesonide (400 mcg/day) for 5 weeks (run-in period); then they were randomized to use budesonide (800 mcg/day--BUD group) or budesonide plus formoterol (400 mcg and 24 mcg/day, respectively--FORMO group) for 9 weeks (treatment period). Home PEF measurements, symptom daily reporting, spirometry, sputum induction (for differential cell counts and sputum cell cultures), and hypertonic saline bronchial challenge test were performed before and after treatments. TNF-alpha, IL-4 and eotaxin-2 levels in the sputum and cell culture supernatants were determined. Morning and night PEF values increased in the FORMO group during the treatment period (p<0.01), from 435+/-162 to 489+/-169 and 428+/-160 to 496+/-173 L/min, respectively. The rate of exacerbations in the FORMO group was lower than in the BUD group (p<0.05). Neutrophil counts in sputum increased in both groups (p<0.05) and leukocyte viability after 48 h-culture increased in the FORMO group (p<0.05). No other parameter changed significantly in either group. This study showed that adding formoterol to budesonide improved home PEF and provided protection from exacerbations, although increase of leukocyte viability in cell culture may be a matter of concern and needs further investigation.

Laboratory animals and respiratory allergies: The prevalence of allergies among laboratory animal workers and the need for prophylaxis

OBJECTIVE: Subjects exposed to laboratory animals are at a heightened risk of developing respiratory and allergic diseases. These diseases can be prevented by simple measures such as the use of personal protective equipment. We report here the primary findings of the Laboratory Animals and Respiratory Allergies Study regarding the prevalence of allergic diseases among laboratory animal workers, the routine use of preventive measures in laboratories and animal facilities, and the need for prevention programs. METHODS: Animal handlers and non-animal handlers from 2 Brazilian universities (University of São Paulo and State University of Campinas) answered specific questionnaires to assess work conditions and symptoms. These subjects also underwent spirometry, a bronchial challenge test with mannitol, and skin prick tests for 11 common allergens and 5 occupational allergens (rat, mouse, guinea pig, hamster, and rabbit). RESULTS: Four hundred fifty-five animal handlers (32±10 years old [mean±SD], 209 men) and 387 non-animal handlers (33±11 years old, 121 men) were evaluated. Sensitization to occupational allergens was higher among animal handlers (16%) than non-animal handlers (3%, p<0.01). Accessibility to personal protective equipment was measured at 85% (median, considering 73 workplaces of the animal handler group). Nineteen percent of the animal handlers indicated that they wear a respirator at all times while handling animals or working in the animal room, and only 25% of the animal handlers had received an orientation about animal-induced allergies, asthma, or rhinitis. CONCLUSION: In conclusion, our data indicate that preventive programs are necessary. We suggest providing individual advice to workers associated with institutional programs to promote a safer work environment. .

Comparison of 4 AM and 4 PM bronchial responsiveness to hypertonic saline in asthma.

Bronchial responsiveness to methacholine or histamine increases at night and may contribute to the mechanisms of nocturnal asthma. Hypertonic saline (HS) is a more clinically relevant stimulus for the diagnosis and assessment of the severity of asthma, but the circadian variation in bronchial responsiveness to hypertonic challenges has not been addressed. The aim of this study was to compare the responsiveness to hypertonic saline at 4:00 AM and at 4:00 PM. Eighteen diurnally active patients (11 women) with asthma, 31 +/- 9 years of age (mean +/- SD) and with a forced expiratory volume in 1 s (FEV(1)) of 79.11% +/- 12.85%, underwent two challenge tests (4:00 AM and 4:00 PM) in random sequence separated by an interval of 7 days. The challenge test consisted of inhalations of 4.5% saline with increasing doses by doubling the duration of nebulization (0.5, 1, 2, 4, and 8 min). The inhalation continued until a drop of 20% in FEV(1) was achieved or total time of 15.5 min. The provocative dose that caused the 20% drop in FEV(1) (PD(20)) was calculated. Differences were found between 4:00 PM and 4:00 AM values for inhalation times [3.80 +/- 3.57 min and 2.19 +/- 2.42 min (p = 0.001), respectively] and for PD(20) [4.94 +/- 6.77 ml and 2.93 +/- 4.74 ml (p = 0.002), respectively]. Eight patients with a home-assessed nocturnal peak expiratory flow (PEF) drop of more than 15% formed the nocturnal asthma group. The behavior of these patients was similar to that of the non-nocturnal asthma group. We conclude that the bronchial responsiveness to HS increases at night.

Morning-to-evening variation in exercise-induced bronchospasm.

BACKGROUND: Exercise is one of the most common triggers of asthmatic symptoms. Many factors, including hyperventilation, determine the prevalence and severity of exercise-induced bronchospasm (EIB). However, the influence of time of day has not been adequately described. OBJECTIVE: We sought to compare morning and evening EIB and minute ventilation during exercise (VE). METHODS: Twenty-two patients with stable asthma and 12 control subjects underwent exercise challenge at 7 am and 6 pm. The time of the first challenge was randomly assigned; the second challenge was performed within 1 week of the first. The primary outcomes were EIB intensity (maximum fall in FEV(1)) and VE. RESULTS: The asthma group exhibited lower EIB values in the morning: 14.8% +/- 3.7% at 7 am vs 21.4% +/- 4.2% at 6 pm (P =.004)-ie, 0.37 +/- 0.09 L vs 0.53 +/- 0.10 L, respectively (P =.002). VE was higher at 7 am (55.4 +/- 4.7 L/min) than at 6 pm (52.4 +/- 4.3 L/min; P =.03). Baseline FEV(1) increased from 2.33 +/- 0.13 L (morning) to 2.49 +/- 0.15 L (evening; P =.04), and a significant correlation between baseline FEV(1) and EIB was found in the evening (r = +0.5; P =.049) but not in the morning. Post-exercise FEV(1) was similar at 7 am (1.96 +/- 0.13 L) and 6 pm (1.97 +/- 0.14 L). For the control group, no changes were detected in FEV(1) fall or VE. CONCLUSION: Baseline airway caliber contributes to the mechanisms of the morning-to-evening EIB enhancement.

Asma brônquica: o presente e o futuro / Bronchial asthma: today and tomorrow

A asma é caracterizada por obstruçäo reversível, inflamaçäo e hiperreatividade brônquicas. O diagnóstico é baseado em informaçöes clínicas e testes de funçäo pulmonar. Os eosinófilos säo uma característica importante da fisiopatologia da asma. Eles produzem fatores quimiotáxicos, broncoconstrictores e vasoativos, que conduzem a hiperreatividade brônquica. Além disso, os eosinófilos danificam o tecido circunvizinho, através da liberaçäo do conteúdo protéico de seus grânulos. As recomendaçöes para o tratamento da asma säo baseadas em quatro componentes: uso de medidas objetivas da funçäo pulmonar para avaliar a gravidade da asma e monitorar o curso da terapia; controle ambiental para evitar ou eliminar fatores precipitantes de sintomas ou crises; terapia farmacológica a longo prazo, para tratar e prevenir inflamaçäo de via aérea e, também, para tratar as agudizaçöes; e educaçäo do paciente, criando uma parceria entre o paciente, a família e o clínico. Os ß2-agonistas säo a classe de drogas mais comumente usadas para o tratamento da asma. Usar essas drogas em demanda é freqüentemente mais aceito e recomendado. Em asma aguda, um ß2-agonista é ainda o medicamento de escolha. Agonistas de açäo prolongada, salmeterol e formoterol, podem diminuir sintomas de asma durante o dia e a noite. A teofilina, cujo uso esteve limitado pela toxicidade, pode recuperar uma posiçäo importante no tratamento da asma, com a descoberta de suas açöes antiinflamatórias. O brometo de ipratrópio, uma droga anticolinérgica, ainda espera um papel definido no tratamento da asma. Os corticoesteróides inalatórios têm efeitos mensuráveis nos simtomas, funçäo pulmonar, reatividade brônquica e inflamaçäo. Os efeitos colaterais limitam a administraçäo sistêmica, mas näo a administraçäo tópica. Preparaçöes mais novas, como budesonida, flunisolida e fluticasona diminuem a incidência de possíveis efeitos colaterais, porque têm uma melhor relaçäo efeito tópico/efeito sistêmico. Medicamentos recentemente lançados incluem os antileucotrienos (anti-LTs), agentes que funcionam bloqueando a interaçäo dos LTs com seus receptores (antagonistas de receptor) ou inibindo a síntese de LTs (inibidores de síntese). Representantes dos antagonistas säo zafirlukast, pranlukast e montelukast. Pranlukast, melhora funçäo pulmonar e sintomas, dependendo da dose. Zileuton, um inibidor de síntese, demonstrou melhorar a funçäo pulmonar, reduzir sintomas, reduzir uso de ß-agonistas e crises de asma.

Abordagem clínica da asma brônquica / Bronchial asthma clinical approach

A asma é caracterizada por inflamaçäo, obstruçäo reversível e hiperreatividade brônquica. Esta revisäo objetiva oferecer aos estudantes de Medicina e médicos, recomendações para o atendimento do paciente asmático, de forma a mostrar as abordagens terapêuticas e sugerir uma proposta, reunindo opiniões de diferentes consensos