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SummaryBackground Workers exposed to laboratory animals have a high risk of developing laboratory animal allergy (LAA). Atopy seems to be the main risk factor for LAA. We hypothesized that occupational sensitization is a better predictor for the development of asthma, rhinitis, and bronchial hyperresponsiveness (BHR) than common sensitization. Objective To investigate the association between occupational sensitization to laboratory animals and clinical outcomes. Methods This was a cross-sectional study performed at two universities on students and employees dealing with small rodents. The subjects were allocated in groups: non-sensitized, common sensitization, or occupational sensitization, according to the results of the skin prick test (SPT). All subjects answered a questionnaire about animal exposures, symptoms, allergic diseases, and underwent spirometry and bronchial challenge test with mannitol. Multivariate analysis was performed using Poisson regression to estimate the prevalence ratio (PR). Results Data from 453 volunteers were analysed. Non-sensitized group comprised 237 subjects; common sensitization group, 142 subjects; and occupational sensitization group, 74 subjects. Occupational sensitization was associated with greater risk for all outcomes studied. When the common sensitization group was reference, skin symptoms had PR of 1.36, 95% confidence interval (CI): 1.01-1.85; wheezing had PR of 1.75, CI 95%: 1.21-2.53; rhinitis had PR of 1.25, 95%: 1.11-1.40; nocturnal dyspnoea had PR of 2.40, 95% CI: 1.31-4.40; bronchial hyperresponsiveness (BHR) had PR of 2.47, 95% CI: 1.50-4.09; and confirmed asthma had PR of 2.65, 95% CI: 1.45-4.85. In addition, the overlap of asthma, rhinitis, and skin symptoms in a same subject was significantly more prevalent in the occupational sensitization group, 16.2% versus 4.9% in the common sensitization group. Conclusion and Clinical Relevance Occupational sensitization is associated with allergic symptoms and respiratory diseases. SPT with occupational allergens along with other parameters may contribute to detection of risk for allergic and respiratory diseases associated with exposure to laboratory animals.

The association between pet ownership and the development of allergic and respiratory diseases has been the aim of several studies, however, the effects of exposure in adults remain uncertain. The aims of the present study were to investigate the prevalence of asthma and lung function status among dog and cat owners. This cross-sectional study was performed at two universities with students and workers who were allocated into 3 groups according to pet ownership in the previous year: cat owners, dog owners, and no pets (control group). Subjects underwent spirometry, bronchial challenge test with mannitol, skin prick tests, and questionnaires about animal exposures and respiratory symptoms. Control group comprised 125 subjects; cat owner group, 51 subjects; and dog owner group, 140 subjects. Cat owners had increased asthma prevalence (defined by symptoms and positive bronchial challenge test), but no changes in lung function compared to the control group. The dog owner group had lower spirometry values (forced expiratory volume in one second and lower forced vital capacity), but similar asthma prevalence, compared to the control group. In the cat owner group, excess of asthma may have an immunological basis, since we found an association with atopy. Although we did not have endotoxin data from volunteers' households, we postulated that low values of lung function were associated to exposure to endotoxins present in environments exposed to dogs.

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.In this cross-sectional study we recruited 908 workers in 2 universities; they underwent a respiratory questionnaire, spirometry, skin prick tests, and MCT.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 FEVMCT 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.

Background Endotoxin from Gram-negative bacteria are found in different concentrations in dust and on the ground of laboratories dealing with small animals and animal houses. Methods Cross-sectional study performed in workplaces of two universities. Dust samples were collected from laboratories and animal facilities housing rats, mice, guinea pigs, rabbits or hamsters and analyzed by the “Limulus amebocyte lysate” (LAL) method. We also sampled workplaces without animals. The concentrations of endotoxin detected in the workplaces were tested for association with wheezing in the last 12 months, asthma defined by self-reported diagnosis and asthma confirmed by bronchial hyperresponsiveness (BHR) to mannitol. Results Dust samples were obtained at 145 workplaces, 92 with exposure to animals and 53 with no exposure. Exposed group comprised 412 subjects and non-exposed group comprised 339 subjects. Animal-exposed workplaces had higher concentrations of endotoxin, median of 34.2 endotoxin units (EU) per mg of dust (interquartile range, 12.6–65.4), as compared to the non-exposed group, median of 10.2 EU/mg of dust (interquartile range, 2.6–22.2) (p

OBJECTIVES The aim of this estudy was to investigate the influence of allergen exposure levels and other risk factors for allergic sensitization, asthma, and bronchial hyperresponsiveness (BHR) in workers exposed to laboratory animals. METHODS This was a cross-sectional study performed at two universities, 123 workplaces with 737 subjects. Dust samples were collected from laboratories and animal facilities housing rats, mice, guinea pigs, rabbits, or hamsters and analyzed by enzyme-linked immunosorbent assay (ELISA) to measure allergen concentrations. We also sampled workplaces without animals. Asthma was defined by both symptoms and BHR to mannitol. The concentrations of allergens were tested for association with a skin prick test, respiratory symptoms, spirometry data, and BHR. This multivariate analysis was performed by using Poisson regression to estimate the relative risk (RR) for the exposed group. RESULTS Our sample comprised students and workers, with 336 subjects in the nonexposed group and 401 subjects in the exposed group. Sixty-nine subjects (17%) had positive results in the skin prick test for animal allergens in the exposed group; in the nonexposed group, 10 subjects had positive results (3%) (p

OBJETIVO: Estudar a associacao entre atopia e variaveis como peso, comprimento e nivel socioeconomico no nascimento e na idade adulta jovem. METODOS: Foram investigados 2.063 individuos em um estudo prospectivo de coorte de nascimento com individuos nascidos em Ribeirao Preto (SP), em 1978/1979, e examinados aos 23-25 anos de idade. Realizaram-se testes cutâneos de puntura (TCP) para oito alergenos comuns no Brasil. Foram considerados atopicos os individuos que apresentaram reacao papular > 3 mm para um ou mais dos oito alergenos testados. A fim de avaliar a associacao entre atopia e variaveis no nascimento e na idade adulta, utilizamos o modelo log-binomial (modelo linear generalizado). RESULTADOS: A prevalencia de TCP positivo foi de 47,6%. O genero masculino esteve associado a aumento do risco de atopia [risco relativo (RR) = 1,18; intervalo de confianca de 95% (IC95%) 1,07-1,30]. O baixo nivel de escolaridade foi um fator de protecao contra atopia, com um RR = 0,74; IC95% 0,62-0,89. A convivencia com um fumante na infância tambem esteve associada a um menor risco de atopia (RR = 0,87; IC95% 0,79-0,96). Peso e comprimento ao nascer, ordem de nascimento, idade materna e restricao de crescimento intrauterino nao estiveram associados a TPC positivo. CONCLUSOES: Este estudo demonstrou que o genero masculino esteve associado a um aumento do risco de atopia. O baixo nivel socioeconomico, estabelecido pelo baixo nivel de escolaridade, foi um fator de protecao contra a atopia. Esses dados estao de acordo com a teoria da higiene.

Inhalation of hypertonic saline (HS) causes bronchoconstriction in asthmatic subjects. Repeated inhalation of HS leads to substantially reduced bronchoconstriction, known as the refractory period. Refractoriness due to different stimuli has also been described (cross-refractoriness). Nocturnal asthma is defined as an increase in symptoms, need for medication, airway responsiveness, and/or worsening of lung function that usually occurs from 4 to 6 am. Our objective was to determine the effect of refractoriness on nocturnal asthma. The challenge test consisted of inhalations of 4.5% saline with increasing durations until a reduction of 20% in forced expiratory volume in 1 s (FEV1) (PD20HS) or total time of 15.5 min. Twelve subjects with nocturnal asthma were challenged with HS at 16:00 and 18:00 h and FEV1 was measured at 4:00 h. One to 2 weeks later, FEV1 was determined at 16:00 and 4:00 h. LogPD20HS at 18:00 h was significantly greater than logPD20HS at 16:00 h, 0.51 +/- 0.50 and 0.69 +/- 0.60 mg, respectively (P = 0.0033). When subjects underwent two HS challenges in the afternoon, mean (+/- SD) FEV1 reduction was 206 +/- 414 mL or 9.81 +/- 17.42%. On the control day (without challenge in the afternoon) FEV1 reduction was 523 +/- 308 mL or 22.75 +/- 15.40% (P = 0.021). Baseline FEV1 values did not differ significantly between the control and study days, 2.48 +/- 0.62 and 2.36 +/- 0.46 L, respectively. The refractory period following HS challenges reduces the nocturnal worsening of asthma. This new concept may provide beneficial applications to asthmatic patients.

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.

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

OBJECTIVE: To develop and validate an asthma knowledge questionnaire for use in adult asthma patients in Brazil. METHODS: A 34-item self-report questionnaire was constructed and administered to adult asthma patients and adult controls. The maximum total score was 34. RESULTS: The questionnaire was shown to be discriminatory, with good reliability and reproducibility. The mean score for asthma patients and controls was, respectively, 21.47 ± 4.11 (range: 9-31) and 17.27 ± 5.11 (range: 7-28; p < 0.001). The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.53, and the Bartlett's test of sphericity demonstrated a satisfactory suitability of the data to factor analysis (p < 0.001). There was no significant difference between the total scores obtained in the first and in the second application of the questionnaire within a two-week interval (p = 0.43). The internal consistency reliability (KR-20 coefficient) was 0.69. CONCLUSIONS: This study has validated an asthma knowledge questionnaire for use in Brazil. OBJETIVO: Desenvolver e validar um questionário de conhecimento em asma para pacientes adultos asmáticos no Brasil. MÉTODOS: Um questionário autoaplicável com 34 itens foi desenvolvido e aplicado em asmáticos e controles adultos. A pontuação total máxima era 34. RESULTADOS: O questionário mostrou-se discriminante, com boa confiabilidade e reprodutibilidade. O escore médio para os asmáticos e controles foi, respectivamente, 21,47 ± 4,11 (variação: 9-31) e 17,27 ± 5,11 (variação: 7-28; p < 0,001). O teste de Kaiser-Meyer-Olkin revelou uma medida de adequação de 0,53, e o teste de esfericidade de Bartlett demonstrou uma adequação satisfatória dos dados para a análise fatorial (p < 0,001). Não houve diferença significativa entre os escores totais obtidos na primeira e na segunda aplicação do questionário, com um intervalo de duas semanas (p = 0,43). O coeficiente de consistência interna (coeficiente KR-20) foi 0,69. CONCLUSÕES: Este estudo validou um questionário de educação em asma para uso no Brasil.

To evaluate knowledge of and techniques for using prescribed inhalation devices among patients with asthma or COPD treated at a tertiary teaching hospital.Patients were assessed after medical visits, and their physicians were blinded to this fact. Patients were asked to demonstrate their inhaler technique and were then interviewed regarding their knowledge of inhalation devices, control of the disease and instructions received during medical visits.We included 120 volunteers: 60 with asthma and 60 with COPD. All of the asthma patients and 98.3% of the COPD patients claimed to know how to use inhaled medications. In the sample as a whole, 113 patients (94.2%) committed at least one error when using the inhalation device. Patients committed more errors when using metered-dose inhalers than when using the dry-powder inhalers Aerolizer (p0.001) or Pulvinal (p0.001), as well as committing more errors when using the Aerolizer inhaler than when using the Pulvinal inhaler (p0.05). Using the metered-dose, Pulvinal and Aerolizer inhalers, the COPD group patients committed more errors than did the asthma group patients (p = 0.0023, p = 0.0065 and p = 0.012, respectively).Although the majority of the patients claimed to know how to use inhalation devices, the fact that 94.2% committed at least one error shows that their technique was inappropriate and reveals a discrepancy between understanding and practice. Therefore, it is not sufficient to ask patients whether they know how to use inhalation devices. Practical measures should be taken in order to minimize errors and optimize treatment.

To determine the prevalence of factors associated with difficult-to-control asthma.Patients with severe asthma were selected from the outpatient asthma clinic of the Ribeirão Preto School of Medicine Hospital das Clínicas. The patients were divided into two groups: controlled severe asthma and difficult-to-control severe asthma. After new attempts to optimize the severe asthma treatment, a questionnaire was applied, and additional tests for factors associated with difficult-to-control asthma, such as environmental and occupational exposure, smoking history, social factors, rhinitis/sinusitis, gastroesophageal reflux disease (GERD), obstructive sleep apnea, congestive heart failure (CHF), pulmonary embolism, cystic fibrosis, vocal cord dysfunction, alpha-1 antitrypsin deficiency, and Churg-Strauss syndrome, were performed.77 patients with severe asthma were selected, of which 47 suffered from hard-to-control asthma, being 68.1% female, with mean age of 44.4 years (+/-14.4), and forced expiratory volume in one second of 54.7% (+/-18.3). The most factors most often associated with difficult-to-control asthma were noncompliance with treatment (68%), rhinitis/sinusitis (57%), GERD (49%), environmental exposure (34%), occupational exposure (17%), smoking history (10%), obstructive sleep apnea (2%), and CHF (2%). At least one of these factors was identified in every case.Noncompliance with treatment was the factor most often associated with difficult-to-control asthma, underscoring the need to investigate comorbidities in the evaluation of patients with this form of the disease.

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.