Risk factors for recurrent wheezing in preterm infants who received prophylaxis with palivizumab / Fatores de risco para sibilância recorrente em crianças pré-termo que receberam profilaxia com palivizumabe

ABSTRACT Objective: To determine the prevalence of recurrent wheezing (RW) in preterm infants who received prophylaxis against severe infection with respiratory syncytial virus (RSV) and to identify genetic susceptibility (atopy or asthma) and risk factors for RW. Methods: This was a cross-sectional study involving preterm infants who received prophylaxis with palivizumab at a referral center in Brazil during the first two years of age. A structured questionnaire was administered in a face-to-face interview with parents or legal guardians. Results: The study included 410 preterm infants (median age = 9 months [0-24 months]). In the sample as a whole, 111 children (27.1%; [95% CI, 22.9-31.5]) had RW. The univariate analysis between the groups with and without RW showed no differences regarding the following variables: sex, ethnicity, maternal level of education, gestational age, birth weight, breastfeeding, number of children in the household, day care center attendance, pets in the household, and smoking caregiver. The prevalence of RW was twice as high among children with bronchopulmonary dysplasia (adjusted OR = 2.08; 95% CI, 1.11-3.89; p = 0.022) and almost five times as high among those with a personal/family history of atopy (adjusted OR = 4.96; 95% CI, 2.62-9.39; p < 0.001) as among those without these conditions. Conclusions: Preterm infants who received prophylaxis with palivizumab but have a personal/family history of atopy or bronchopulmonary dysplasia are more likely to have RW than do those without these conditions.

RESUMO Objetivo: Determinar a prevalência de sibilância recorrente (SR) em crianças pré-termo que receberam profilaxia contra infecção grave pelo vírus sincicial respiratório (VSR) e identificar susceptibilidade genética (atopia ou asma) e fatores de risco para SR. Métodos: Estudo transversal envolvendo crianças pré-termo que receberam profilaxia com palivizumabe em um centro de referência no Brasil durante os primeiros dois anos de vida. Um questionário estruturado foi aplicado em entrevista presencial com os pais ou responsáveis. Resultados: O estudo incluiu 410 crianças pré-termo (mediana de idade = 9 meses [0-24 meses]). Na amostra total, 111 crianças (27,1%; IC95%: 22,9-31,5) apresentavam SR. A análise univariada entre os grupos com e sem SR não mostrou diferenças em relação às seguintes variáveis: sexo, etnia, escolaridade materna, idade gestacional, peso ao nascer, aleitamento materno, número de crianças no domicílio, frequência em creche, presença de animais de estimação no domicílio e cuidador tabagista. A prevalência de SR foi duas vezes maior entre crianças com displasia broncopulmonar (OR ajustada = 2,08; IC95%: 1,11-3,89; p = 0,022) e quase cinco vezes maior entre aquelas com história pessoal/familiar de atopia (OR ajustada = 4,96; IC95%: 2,62-9,39; p < 0,001) do que entre aquelas sem essas condições. Conclusões: Crianças pré-termo que receberam profilaxia com palivizumabe, mas apresentam história pessoal/familiar de atopia ou displasia broncopulmonar, têm maior probabilidade de apresentar SR do que aquelas sem essas condições.

The use of probiotics as a supplementary therapy in the treatment of patients with asthma: a pilot study and implications

OBJECTIVES: Evaluate the use of probiotics as an additional therapy in the treatment of children and adolescents with asthma in Belo Horizonte, MG-Brazil. METHODS: A pilot longitudinal, experimental and nonrandomized study with 30 patients from six to 17 years old from Belo Horizonte. In the baseline appointment, all patients received beclomethasone, and one group also received a probiotic containing Lactobacillus reuteri (n=14). The patients were reassessed after at least 60 days with the Asthma Control Test, spirometry and self-report of the symptoms they experienced associated with asthma. RESULTS: A predominance of male patients (56.7%) and a mean age of 10.6 years were observed. The groups using probiotics did not differ in terms of sex, age or atopy. In the longitudinal evaluation, an increase in the Asthma Control Test scores and a reduction in the number of symptoms were observed in the probiotic group. There was an increase in the peak expiratory flow among those who used probiotics. CONCLUSIONS: This pilot study supports the hypothesis that the administration of probiotics as a supplementary therapy for the treatment of children and adolescents with asthma improves the clinical condition of the patients. Further studies are needed to confirm the efficacy of probiotics in asthma treatment.

Principales aeroalérgenos en rinoconjuntivitis alérgica en la ciudad de Temuco, Chile / Aeroallergens causing rhinoconjunctivitis

Background: Allergic rhinoconjunctivitis (ARC) has a prevalence of 30% in industrialized countries. For an accurate diagnosis and treatment, it is crucial to identify the causative aeroallergen. Aim: To evaluate aeroallergen sensitization in adults with ARC in the city of Temuco, Chile. Patients and Methods: A skin test against the main aeroallergens present in Temuco was carried out in patients aged 15 to 64 years with ARC diagnosed by medical examination and the Score For Allergic Rhinitis. Results: At least one aeroallergen sensitization was present in 234 (62.4%) out of 375 patients. Pollen-sensitized patients were positive mainly for Grasses (44.4%), Plantago (27.8%), Cynodon (26.1%), Sorrel (23.5%), Birch (14.9%), Nothofagus obliqua (13.3%) and Alder (11.1%). Dust mites were the most common non-pollinic sensitizing aeroallergens, including Dermatophagoides pteronyssinus (70.1%) and Dermatophagoides farinae (62.8%). Conclusions: According to our results, skin tests in the city of Temuco should include at least dust mites, pollens of Grasses, Plantago, Cynodon, Sorrel, Birch, Nothofagus obliqua and Alder, because these allergens account for 93% of ARC cases in this city.

Asma alérgica e não alérgica apresentam diferentes características fenotípicas e genotípicas / Allergic and non-allergic asthma have different phenotypic and genotypic characteristics

Objetivo: A identificação dos fenótipos da asma permite uma melhor compreensão e abordagem desta doença heterogênea. Muitos estudos têm demonstrado associação entre os antígenos leucocitários humanos (HLA) e asma em diversas populações, porém os resultados são inconclusivos e raramente consideram uma doença com diferentes fenótipos. O objetivo deste estudo foi caracterizar os fenótipos alérgico e não alérgico da asma e avaliar possíveis associações com o sistema HLA. Métodos: Um total de 190 pacientes com asma foram prospectivamente acompanhados durante dois anos. Foram divididos em dois grupos, asma alérgica e não alérgica, de acordo com a história clínica e os resultados do teste cutâneo de puntura e da pesquisa da IgE sérica específica. O grupo controle foi composto por 297 doadores falecidos de órgãos sólidos. As características de cada grupo e a tipificação dos HLA classe I e II foram avaliadas e comparadas. Resultados: O estudo mostrou diferentes características entre os fenótipos estudados. Os pacientes com asma não alérgica relataram uma idade mais tardia de início dos sintomas da doença e maior frequência de história sugestiva de intolerância aos anti-inflamatórios não esteroidais. O grupo asma alérgica apresentaram IgE sérica total elevada, presença de dermatite atópica e rinoconjuntivite mais frequente e, inesperadamente, maior gravidade da doença. Novas associações entre os genótipos HLA e os fenótipos alérgico e não alérgico da asma foram identificados. Os genótipos HLA-B*42, HLA-C*17, HLA-DPA1*03 e HLA-DPB1*105 foram associados com a asma alérgica, e o HLA-B*48 com o fenótipo não alérgico. A presença do haplótipo HLA-DPA1*03 DQA*05 foi associado com asma alérgica, e a presença do HLA-DPA1*03 e ausência do HLA-DQA*05 com a asma não alérgica. Conclusões: A asma alérgica e não alérgica apresentaram diferentes características fenotípicas e genotípicas. Novas associações entre os fenótipos e o sistema HLA classe I e II foram identificadas.

Objective: The identification of asthma phenotypes allows a better understanding and management of this heterogeneous disease. Studies have reported associations between human leukocyte antigens (HLA) and asthma in different populations, but results have been inconclusive and rarely take into consideration the distinct disease phenotypes. The objectives of this study were to characterize allergic and non-allergic asthma phenotypes and to evaluate possible associations with the HLA system. Methods: A total of 190 patients with asthma were prospectively followed during two years. They were divided into two groups, allergic and non-allergic asthma, according to clinical history and the results of skin prick testing and serum-specific IgE measurement. The control group comprised 297 deceased donors of solid organs. The characteristics of each group and HLA class I and II genotypes were assessed and compared. Results: The study revealed different characteristics between the phenotypes studied. Nonallergic patients were older at the onset of asthma symptoms and had a higher rate of history of intolerance to non-steroidal antiinflammatory drugs. Allergic patients showed higher total serum IgE levels, reported atopic dermatitis and rhinoconjunctivitis more frequently, and, unexpectedly, showed greater disease severity. New associations between HLA genotypes and the allergic/non-allergic asthma phenotypes were identified. HLA-B*42, HLA-C*17, HLADPA1* 03, and HLA-DPB1*105 genotypes were associated with allergic asthma, and HLA-B*48, with the non-allergic phenotype. The presence of haplotype HLA-DPA1*03 DQA*05 was associated with allergic asthma, and the presence of HLA-DPA1*03 and absence of HLA-DQA*05, with non-allergic asthma. Conclusion: Allergic and non-allergic asthma have distinct phenotypic and genotypic characteristics. New associations between asthma phenotypes and HLA class I and II were identified.

Pathophysiology, Causes and Treatment of Chronic Cough in Adults: Literature Review / 대한이비인후과학회지

Chronic cough is a common symptom and the etiology of which can be challenging to diagnose. The key to successful management is to establish a diagnosis and to treat the cause of cough. Asthma, gastro-esophageal reflux, and postnasal drip syndrome have been thought to be most common causes of chronic cough. Various causes such as lung diseases (sarcoidosis, pertussis), obstructive sleep apnea, drug (angiotensin-converting enzyme inhibitor), and psychological status can induce chronic cough. However, many chronic cough patients do not have an identifiable cause. We need to understand the mechanisms underlying central and peripheral sensitization, how they interact with cough triggers and their relationship with the sensations that drive the urge to cough, and the subsequent motor cough response in chronic cough. Heightened cough reflex sensitivity is persistent and their cough is unexplained in many patients. In most patients who visited otorhinolaryngoloy clinics, it is possible to manage a majority of chronic cough patients successfully using a protocol based on presenting symptoms and therapeutic trials for the common causes of cough. However, there are few therapeutic options for patients with unexplained chronic cough. There is a pressing need to understand the physiological basis of unexplained chronic cough and to develop novel antitussive drugs that down regulate cough reflex sensitivity.

Total IgE plasma levels vary according to gender and age in Brazilian patients with allergic rhinitis

OBJECTIVE: Allergic rhinitis is a disease that affects the upper airways and causes inflammation of the nasal mucosa and it is mediated by IgE antibodies produced after sensitization to environmental allergens. Previous reports have indicated that this disease affects males more often than females. The objective of this study was to verify whether total IgE plasma levels vary between genders in patients suffering from allergic rhinitis. METHODS: A total of 171 adult patients suffering from allergic rhinitis (55 males and 116 females) were enrolled. Total IgE plasma levels were determined using commercial kits, with 140 IU/mL considered as a reference value. The mean total IgE plasma levels were compared according to gender and age. RESULTS: The mean age of the overall patient group with allergic rhinitis was 38.4±19.0 years and a significant difference in age was observed between genders (males: 32.2±17.8 years; females: 41.4±18.9 years; p = 0.0027). Additionally, the mean total IgE plasma levels were higher in males (413.0±143.0 IU/mL) than in females (147.9±98.0 IU/mL) (p<0.0001). These differences persisted even when males and females were stratified by age (up to or older than 20 years of age). CONCLUSIONS: In conclusion, total IgE plasma levels are higher in young adult males than in females suffering from allergic rhinitis. Evaluating total IgE plasma levels can be useful to identify patients at risk of allergic rhinitis in areas with low industrial pollution. .

Capsaicin cough sensitivity is related to the older female predominant feature in chronic cough patients

PURPOSE: The present study aimed to examine the age and gender distributions among chronic cough patients referred to a tertiary cough clinic in Korea, and to investigate clinical factors related to the demographic findings. METHODS: Study participants were unselectively recruited from adult chronic cough patients who attended the cough clinic for the first time during one year. To validate their representativeness, their age and gender distributions were compared to the entire chronic cough population, or with those presenting with other chronic disease. Data from the baseline investigations were analyzed to identify clinical factors related to the demographic findings. RESULTS: A total of 272 chronic cough patients were included. They had a middle-aged female predominant feature (mean age: 52.8+/-15.7 years and female 69.1%). Their age and gender distributions were almost identical to the entire chronic cough population, but were distinct from patients with hypertension. Among clinical factors, the older female predominance was associated with enhanced capsaicin cough sensitivity, and also with the presence of 'cough by cold air' symptom. Allotussia and laryngeal paresthesia were highly common in chronic cough patients, affecting 94.8% and 86.8% of them, respectively. CONCLUSIONS: The present study demonstrated older female predominance among adult chronic cough patients attending a referral cough clinic in Korea. The demographic features were significantly associated with the capsaicin cough responses and also potentially with allotussia (particularly cold air as the trigger). These findings suggest a role of cough reflex sensitization in the pathophysiology of chronic cough in adults.

Changing the paradigm for cough: does 'cough hypersensitivity' aid our understanding?

Chronic cough is a common reason for patients to seek medication attention. Over the last few decades, we have experienced significant clinical success by applying the paradigm of 'evaluating and treating the causes for chronic cough'. However, we still ask ourselves 'what underlies chronic cough. Indeed in a considerable proportion of patients cough is idiopathic, or unexplained despite vigorous evaluation. Commonly associated conditions such as rhinitis, eosinophilic bronchitis, asthma, or gastroesophageal acidic reflux may not be fundamental to cough, and thus may be triggers rather than causes. The cardinal feature of chronic cough is persistent upregulation the cough reflex, which may be driven by complex interactions between biologic, neurologic, immunologic, genetic, comorbid, and environmental factors. We suggest the new paradigm 'cough hypersensitivity syndrome' should finally bring us further advances in understanding and management of chronic cough.

Pulmão dos criadores de aves complicado por nocardiose pulmonar / Bird fancier's lung complicated by pulmonary nocardiosis

Relatamos o caso de um paciente de 84 anos que foi hospitalizado devido a tosse persistente e dispneia. A radiografia de tórax inicial revelou infiltrados pulmonares. Nocardia asteroides foi detectada no escarro, e o paciente foi tratado com antibióticos; entretanto, seus sintomas não melhoraram por completo. O paciente foi hospitalizado várias vezes, e os sintomas reapareceram após cada alta. Houve a suspeita de pneumonite de hipersensibilidade, sendo o paciente diagnosticado com pulmão dos criadores de aves. É provável que a nocardiose pulmonar se desenvolva em pacientes com doenças pulmonares crônicas, como DPOC, e em hospedeiros imunossuprimidos. Até onde sabemos, este é o primeiro relato de um caso de pulmão dos criadores de aves complicado por nocardiose pulmonar.

We report the case of an 84-year-old male who was admitted to the hospital with persistent cough and dyspnea. An initial chest X-ray revealed pulmonary infiltrates. Nocardia asteroides was detected in sputum, and the patient was treated with antibiotics. However, his symptoms did not completely resolve. He was admitted multiple times, and his symptoms relapsed after every discharge. He was finally suspected of having hypersensitivity pneumonitis and was diagnosed with bird fancier's lung. Pulmonary nocardiosis is likely to develop in patients with chronic pulmonary disorders, such as COPD, as well as in immunosuppressed hosts. To our knowledge, this is the first report of a case of bird fancier's lung complicated by pulmonary nocardiosis.

Effects of propofol on airway hyperresponsiveness and airway inflammation of asthmatic mice / 中华麻醉学杂志

Objective To investigate the immunoregulatory effects of propofol on airway hyperresponsiveness,airway inflammation and Thl/Th2 ratio in the asthmatic mice.Methods One hundred female BALB/c mice,aged 6-8 weeks,weighing 18-20 g,were randomly divided into 5 groups (n =20,each):control group (normal saline i.p.,group C),asthma group (group A),low-dose propofol (50 mg/kg i.p.,group LP),medium-dose propofol (100 mg/kg i.p.,group MP) and high-dose propofol (150 mg/kg i.p.,group HP).Mice of groups A,LP,MP and HP were sensitized with ovalbumin (OVA),mice of group C were sensitized with normal saline.24 h after the last challenge,animals were sacrificed by lethal dose of pentobarbital sodium.Blood and bronchoalveolar lavage fluid (BALF) were collected for determination of serum OVA-specific IgE and the levels of cytokines (IL-4,IL-5 and IFN-γ) in the BALF.Airway responsiveness was measured by the forced-oscillation technique and histological inflammation scores were measured by staining with hematoxylin and eosin.Results Propofol (group LP and group MP) attenuated airway hyperresposiveness to the muscarinic agonist methacholine in OVA-induced asthma.Different doses of propofol (group LP,group MP and group HP) decreased eosinoplils influx in lungs.In addition,propofol treatment reduced expression of IL-4,IL-5 and serum OVA-specific IgE and increased the ratio of IFN-γ/IL-4.Conclusion The study demonstrates a potential protective value of propofol in alleviating airway inflammation,up-regulating Th1/Th2 ratio and attenuating airway hyperresposiveness in the asthmatic mice.

Evidence of an association between the O blood group and allergic rhinitis

OBJECTIVE: The aim of this study was to verify if ABO phenotypes are associated with allergic rhinitis. METHODS: 168 patients with allergic rhinitis and 168 control individuals from the same geographical region and paired by gender and age were enrolled in the study. ABO phenotypes were identified in red blood cells using the hemagglutination technique. The Fisher exact and chi-squared tests were employed to compare proportions. Statistical significance was set for an alpha error of 5 percent (p-value < 0.05). RESULTS: The overall differences in the frequencies of the ABO phenotypes of patients and controls were marginal (χ2: 7.569; degrees of freedom (DF): 3; p-value = 0.055) however the O blood group was associated with allergic rhinitis (χ2: 5.764; DF: 1; p-value = 0.016; OR: 1.735; CI 95 percent: 1.127-2.673). The differences in the frequencies of the O phenotype in patients and controls were statistically different for men (χ2: 8.520; DF: 1; p-value = 0.003) but not for women (χ2: 0.6375; DF: 1; p-value = 0.4246). The A phenotype was associated with protection (OR: 0.4385; CI 95 percent: 0.2043-0.9415; p-value = 0.049) and the O phenotype was associated with susceptibility (OR = 2.789; CI 95 percent: 1.385-5.616; p-value = 0.005) to allergic rhinitis only for men. CONCLUSION: The O blood group phenotype is associated with allergic rhinitis in male but not in female patients.

Bronchial provocation tests in clinical practice / Teste de broncoprovocação na prática clínica

Bronchial hyperresponsiveness, which consists of an exaggerated response of the airways to bronchoconstrictor stimuli, is one of the main characteristics of asthma, presented in nearly all asthmatic patients. Bronchial hyperresponsiveness may also be present in other diseases, such as allergic rhinitis, chronic obstructive pulmonary disease, cystic fibrosis, heart failure and respiratory infection, and with some medications, such as β-blockers. Bronchial provocation tests (also known as bronchial challenges) are used to evaluate bronchial responsiveness. These tests have become increasingly used over the last 20 years, with the development and validation of accurate, safe and reproducible tests, and with the publication of well-detailed protocols. Several stimuli can be used in a bronchial challenge, and they are classified as direct and indirect stimuli. There are many indications for a bronchial challenge. In this review, we discuss the main differences between direct and indirect stimuli, and the use of bronchial challenges in clinical practice, especially for confirming diagnoses of asthma, exercise-induced bronchoconstriction and cough-variant asthma, and for use among elite-level athletes.

Hiperresponsividade brônquica, caracterizada por uma resposta exagerada das vias aéreas a um estímulo broncoconstritor, é uma das principais características da asma, presente em praticamente todos pacientes asmáticos. A hiperresponsividade brônquica pode estar presente também em outras doenças, como rinite alérgica, doença pulmonar obstrutiva crônica, fibrose cística, insuficiência cardíaca, infecção respiratória e com o uso de algumas medicações, como β-bloqueadores. Os testes de broncoprovocação são utilizados para determinação da responsividade brônquica, e têm sido cada vez mais utilizados nos últimos 20 anos com o desenvolvimento e validação de testes acurados, seguros e reprodutíveis e com a publicação de protocolos bem detalhados. Diversos estímulos podem ser utilizados em um teste de broncoprovocação, sendo classificados em estímulos diretos e indiretos. Existem inúmeras indicações para um teste de broncoprovocação. Nesta revisão, nós discutimos as principais diferenças dos estímulos diretos e indiretos e o uso desses testes na prática clínica, especialmente para a confirmação de asma, broncoconstrição induzida por exercício, tosse variante de asma e em atletas de elite.

IL-12-STAT4-IFN-gamma axis is a key downstream pathway in the development of IL-13-mediated asthma phenotypes in a Th2 type asthma model

IL-4 and IL-13 are closely related cytokines that are produced by Th2 cells. However, IL-4 and IL-13 have different effects on the development of asthma phenotypes. Here, we evaluated downstream molecular mechanisms involved in the development of Th2 type asthma phenotypes. A murine model of Th2 asthma was used that involved intraperitoneal sensitization with an allergen (ovalbumin) plus alum and then challenge with ovalbumin alone. Asthma phenotypes, including airway-hyperresponsiveness (AHR), lung inflammation, and immunologic parameters were evaluated after allergen challenge in mice deficient in candidate genes. The present study showed that methacholine AHR and lung inflammation developed in allergen-challenged IL-4-deficient mice but not in allergen-challenged IL-13-deficient mice. In addition, the production of OVA-specific IgG2a and IFN-gamma-inducible protein (IP)-10 was also impaired in the absence of IL-13, but not of IL-4. Lung-targeted IFN-gamma over-expression in the airways enhanced methacholine AHR and non-eosinophilic inflammation; in addition, these asthma phenotypes were impaired in allergen-challenged IFN-gamma-deficient mice. Moreover, AHR, non-eosinophilic inflammation, and IFN-gamma expression were impaired in allergen-challenged IL-12Rbeta2- and STAT4-deficient mice; however, AHR and non-eosinophilic inflammation were not impaired in allergen-challenged IL-4Ralpha-deficient mice, and these phenomena were accompanied by the enhanced expression of IL-12 and IFN-gamma. The present data suggest that IL-13-mediated asthma phenotypes, such as AHR and non-eosinophilic inflammation, in the Th2 type asthma are dependent on the IL-12-STAT4-IFN-gamma axis, and that these asthma phenotypes are independent of IL-4Ralpha-mediated signaling.

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.