Local anaesthetic medication for the treatment of asthma

It is presumed that drugs able to prevent bronchial spasm and/or inflammation may have therapeutic potential to control asthma symptoms. The local anaesthetic lidocaine has recently received increased attention as an alternative form of treatment for asthmatic patients. This paper reviews the major findings on the topic and summarizes the putative mechanisms underlying the airway effects of local anaesthetic agents. We think that lidocaine extends the spectrum of options in asthma therapy, probably by counteracting both spasmogenic and inflammatory stimuli in the bronchial airways. The possibility of development of new anti-asthma compounds based on the synthesis of lidocaine derivatives is also on the horizon.

Uso da máscara laríngea descartável em adenotonsilectomias

JUSTIFICATIVA E OBJETIVOS: A intubação traqueal associada a operações das vias aéreas faz com que complicações como laringoespasmo, broncoespasmo e períodos de redução da saturação de oxigênio sejam frequentemente relatados em adenotonsilectomias, procedimento que, por sua natureza, eleva a incidência de tais complicações. O objetivo deste estudo foi analisar a ocorrência de problemas respiratórios comparando-se o uso da máscara laríngea (ML) descartável com a intubação orotraqueal em adenotonsilectomias. MÉTODOS: Foram avaliados 204 pacientes pediátricos submetidos a anestesia geral para adenotonsilectomias e alocados em dois grupos, aleatoriamente: grupo Cânula Traqueal (CT, n = 100) e grupo Máscara Laríngea (ML, n = 104). Foram observados os níveis de saturação de pulso de oxigênio (SpO2) após a indução anestésica (SpO2-1), após o estabelecimento de campo operatório (SpO2-2), ao término do procedimento cirúrgico (SpO2-3), três minutos após a retirada do dispositivo respiratório (SpO2-4) e na admissão da sala de recuperação anestésica (SpO2-5). As complicações respiratórias foram relatadas. RESULTADOS: Os valores médios e os desvios padrão de SpO2 nos grupos CT e ML foram, respectivamente: SpO2-1: 98,9 ± 1,0 e 98,7 ± 0,8 (p > 0,25); SpO2-2: 97,4 ± 1,0 e 94,9 ± 4,3 (p < 0,001); SpO2-3: 96,9 ± 1,1 e 97,2 ± 1,1 (p = 0,037); SpO2-4: 91,7 ± 9,0 e 95,2 ± 2,2 (p < 0,001); SpO2-5: 94,0 ± 2,1 e 95,8 ± 2,6 (p < 0,001). No grupo ML, em 12 pacientes, foi necessária alguma manobra para ajuste do dispositivo e correção de vazamento durante o ato operatório. A ML foi substituída pela CT em quatro pacientes. As complicações respiratórias foram similares entre os grupos. CONCLUSÕES: Adenotonsilectomias em pacientes pediátricos com o emprego da ML, em comparação com a CT, resulta em menores valores de SpO2 intraoperatórios e, eventualmente, necessidade de substituição da ML pela CT. Apesar de a ML viabilizar a cirurgia, pela segurança, o uso da CT é preferível.

Increased myoepithelial cells of bronchial submucosal glands in fatal asthma

Background: Fatal asthma is characterised by enlargement of bronchial mucous glands and tenacious plugs of mucus in the airway lumen. Myoepithelial cells, located within the mucous glands, contain contractile proteins which provide structural support to mucous cells and actively facilitate glandular secretion. Objectives: To determine if myoepithelial cells are increased in the bronchial submucosal glands of patients with fatal asthma. Methods: Autopsied lungs from 12 patients with fatal asthma (FA), 12 patients with asthma dying of non-respiratory causes (NFA) and 12 non-asthma control cases (NAC) were obtained through the Prairie Provinces Asthma Study. Transverse sections of segmental bronchi from three lobes were stained for mucus and smooth muscle actin and the area fractions of mucous plugs, mucous glands and myoepithelial cells determined by point counting. The fine structure of the myoepithelial cells was examined by electron microscopy. Results: FA was characterised by significant increases in mucous gland (p = 0.003), mucous plug (p = 0.004) and myoepithelial cell areas (p = 0.017) compared with NAC. When the ratio of myoepithelial cell area to total gland area was examined, there was a disproportionate and significant increase in FA compared with NAC (p = 0.014). Electron microscopy of FA cases revealed hypertrophy of the myoepithelial cells with increased intracellular myofilaments. The NFA group showed changes in these features that were intermediate between the FA and NAC groups but the differences were not significant. Conclusions: Bronchial mucous glands and mucous gland myoepithelial cell smooth muscle actin are increased in fatal asthma and may contribute to asphyxia due to mucous plugging.

Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

Anti-IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti-IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti-IgE on allergen-induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double-blind, placebo-controlled study. Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti-IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC(20)) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC(20), inflammatory cells in biopsies and sputum were assessed. Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti-IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4-0.5%) and postallergen biopsies (15-2 cells/0.1 mm(2)) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high-affinity IgE receptor and CD4+ cells were decreased within the anti-IgE group. There were no significant differences for PC(20) methacholine. The response to inhaled allergen in asthma is diminished by anti-IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE-bearing cells postallergen without changing PC(20) methacholine. This suggests that the benefits of anti-IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE-bearing cells.

Individual risk prediction of nodal and distant metastasis for patients with typical bronchial carcinoid tumors

Objective: Bronchial typical carcinoid tumors are tow-grade malignancies. However, metastases are diagnosed in some patients. Predicting the individual risk of these metastases to determine patients eligible for a radical lymphadenectomy and patients to be followed-up because of distant metastasis risk is relevant. Our objective was to screen for predictive criteria of bronchial typical carcinoid tumor aggressiveness based on a logistic regression model using clinical, pathological and biomolecular data. Methods: A multicenter retrospective cohort study, including 330 consecutive patients operated on for bronchial typical carcinoid tumors and followed-up during a period more than 10 years in two university hospitals was performed. Selected data to predict the individual risk for both nodal and distant metastasis were: age, gender, TNM staging, tumor diameter and location (central/peripheral), tumor immunostaining index of p53 and Ki67, Bcl2 and the extracellular density of neoformed microvessels and of collagen/elastic extracellular fibers. Results: Nodal and distant metastasis incidence was 11% and 5%, respectively. Univariate analysis identified all the studied biomarkers as related to nodal metastasis. Multivariate analysis identified a predictive variable for nodal metastasis: neo angiogenesis, quantified by the neoformed pathological microvessels density. Distant metastasis was related to mate gender. Discussion: Predictive models based on clinical and biomolecular data could be used to predict individual risk for metastasis. Patients under a high individual risk for lymph node metastasis should be considered as candidates to mediastinal lymphadenectomy. Those under a high risk of distant metastasis should be followed-up as having an aggressive disease. Conclusion: Individual risk prediction of bronchial typical carcinoid tumor metastasis for patients operated on can be calculated in function of biomolecular data. Prediction models can detect high-risk patients and help surgeons to identify patients requiring radical lymphadenectomy and help oncologists to identify those as having an aggressive disease requiring prolonged follow-up. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Effects of inducible nitric oxide synthase inhibition in bronchial vascular remodeling-induced by chronic allergic pulmonary inflammation

Vascular remodeling is an important feature in asthma pathophysiology. Although investigations suggested that nitric oxide (NO) is involved in lung remodeling, little evidence established the role of inducible NO synthase (iNOS) isoform in bronchial vascular remodeling. The authors investigated if iNOS contribute to bronchial vascular remodeling induced by chronic allergic pulmonary inflammation. Guinea pigs were submitted to ovalbumin exposures with increasing doses (1 similar to 5 mg/mL) for 4 weeks. Animals received 1400W (iNOS-specific inhibitor) treatment for 4 days beginning at 7th inhalation. Seventy-two hours after the 7th inhalation, animals were anesthetized, mechanical ventilated, exhaled NO was collected, and lungs were removed and submitted to picrosirius and resorcin-fuchsin stains and to immunohistochemistry for matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and transforming growth factor-beta (TGF-beta). Collagen and elastic fiber deposition as well as MMP-9, TIMP-1, and TGF-beta expression were increase in bronchial vascular wall in ovalbumin-exposed animals. The iNOS inhibition reduced all parameters studied. In this model, iNOS inhibition reduced the bronchial vascular extracellular remodeling, particularly controlling the collagen and elastic fibers deposition in pulmonary vessels. This effect can be associated to a reduction on TGF-beta and on metalloproteinase-9/TIMP-1 vascular expression. It reveals new therapeutic strategies and some possible mechanism related to specific iNOS inhibition to control vascular remodeling.

Intranasal Corticosteroid Administration Reduces Nonspecific Bronchial Hyperresponsiveness and Improves Asthma Symptoms

Introduction. Rhinitis and asthma are currently recognized as manifestations of a single syndrome, the chronic allergic respiratory syndrome. Nearly all individuals with asthma have rhinitis, and severe rhinitis has been associated with worse outcomes in asthma patients. Intranasal treatment has been reported to be beneficial for the lower airways. Methods. This was a randomized, double-blind, placebo-controlled study. The objective was to evaluate the effects that treatment with intranasal beclomethasone dipropionate (BDP; 400 g/d) has on nasal and bronchial symptoms, as well as on lung function test results and bronchial responsiveness to histamine in patients with allergic rhinitis and asthma. We evaluated 33 patients, divided into two groups: treatment (n = 17); and placebo (n = 16). Over the course of the 125-day study period, each patient reported daily rhinitis and asthma symptoms, as well as the need for additional medication. All patients were submitted to spirometry and histamine challenge at baseline and at each subsequent evaluation (on days 50 and 75). Results. In comparison with the patients in the placebo group, those in the BDP treatment group presented significantly fewer nasal symptoms on day 50 and fewer asthma symptoms on day 75 (p 0.01 for both); required rescue medications less often; and presented a significantly lower degree of bronchial responsiveness to histamine on day 75 (p 0.01). Conclusion. In this study, intranasal BDP was effective in treating rhinitis as well as asthma. The benefits for the lower airways were observed only after prolonged treatment and might be better evaluated through nonspecific bronchial challenge.

Bronchial Complications Following Lung Transplantation

Introduction. Bronchial complications owing to the airway anastomosis in lung transplantation are important causes of morbidity and mortality. They occur in up to 27% of cases as defined by stenosis, necrosis, and dehiscence. Treatment depends on the type of complication. Objective. To report our experience to treat this complication. Methods. Between 2000 and 2007, we performed 71 lung transplants of which 36 were bilateral. The total number of anastomoses was 107:52 to the right and 55 to the left. The telescoping technique was initially used (14 initial unilateral transplants), and after October, 2003 it was changed to an end-to-end anastomosis (57 transplants and 93 anastomoses). Results. Eight patients developed bronchial complications including two that were bilateral. There were 4 stenosis, 3 dehiscences, and 3 necrosis complications (9.4%). The complication rate for telescoping anastomosis was 21.4%, and for the end-to-end technique, 7.5%. The treatment of the stenosis used metallic or plastic self-expandable stents. Two bronchial dehiscences resulted in case of bronchopleural fistulae, empyema, and death; the other patient experienced spontaneous resolution. Concerning bronchial necrosis, I patient developed fistulization to the pulmonary artery and massive hemoptysis, and the other with bilateral necrosis, a spontaneous resolution. Conclusion. Our bronchial anastomosis complication rate was comparable with that in other reports. The rate for the telescoping technique was greater compared with the end-to-end technique. The treatment of bronchial stenosis with a self-expandable prosthesis showed good results.

Effects of cyclosporine a and bronchial transection on mucociliary transport in rats

Background. Posttransplant infection remains the leading cause of morbidity and mortality after lung transplantation. We hypothesized that bronchial transection and immunosuppression by cyclosporine both play a key role in the impairment of airway mucociliary clearance, a basic defense system. Methods. Sixty-four rats were assigned to four groups of 16 each according to surgical procedure and drug therapy as follows: sham-operated and saline solution; bronchial transection and saline solution; sham-operated and cyclosporine; bronchial transection and cyclosporine (10 mg/kg/day). Eight animals from each group were euthanized on postoperative day 30 or 90. In vitro mucus transportability, in situ mucociliary transport, and ciliary beating frequency were measured. Results. There was a significant impairment (p < 0.001) on ciliary beating frequency due to either bronchial transection or cyclosporine therapy. In vitro transportability was impaired only in cyclosporine-treated groups (p < 0.001). In situ mucociliary transport was reduced in cyclosporine-treated animals as well as in those that underwent bronchial transection (p < 0.001). This impairment was significantly recovered 90 days after operation. In contrast, the effects of cyclosporine did not change over 90 days of treatment. Conclusions. These results support our hypothesis that mucociliary clearance is impaired after bronchial transection and cyclosporine therapy. Further studies are necessary to relate this finding with posttransplant infection and also to test some drugs aiming to protect airway mucociliary system.

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 FEV1, FEF25-75%, 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 FEV1 (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.

Incremental yield of bronchial washing for diagnosing smear-negative pulmonary tuberculosis

OBJECTIVE To assess the increased diagnostic yield for pulmonary tuberculosis using bronchial washing cultures compared with sputum cultures. METHODS Study conducted with 61 adults in Lima, Peru, from January 2006 to December 2007. The yield of sputum cultures was compared with the yield of acid-fast bacilli smears and cultures of bronchial washing for diagnosing pulmonary tuberculosis in suspected cases of clinical tuberculosis with negative acid fast bacilli sputum smears. RESULTS Twenty seven (95%CI 32;58) of the cases were eventually diagnosed with smear-negative pulmonary tuberculosis. Bronchial washing samples detected 23 (95%CI 72;99) of the smear-negative pulmonary tuberculosis cases compared with 15 (95%CI 37;74) for sputum cultures (p = 0.02). The incremental diagnostic yield of acid fast bacilli smear and culture of bronchial washing specimens over sputum culture was 44% (95%CI 25;65). CONCLUSIONS In function of the epidemiological context and the resources available, bronchoscopy should be deployed as part of a comprehensive work up that optimizes smear-negative pulmonary tuberculosis diagnosis and minimizes risk and costs.

Exposição de pequenos animais à hiperóxia: um modelo para estudo do papel do músculo liso na hiper reactividade brônquica = Hyperoxia - a model to syudy the role of airway smooth muscle on bronchial hyperresponsiveness

Revista Portuguesa de Pneumologia. VIII(3): 223-235.

The contribution of cellblock – histogel – in bronchial washing samples

Introduction: The cellblock is a technique that enables the pathologist to study the morphological detail of residual samples and can be used when it is necessary to perform additional diagnostic techniques. Objective: Demonstrate the processing of bronchial washings in liquid based cytology to cellblock using HistoGel in residual samples, evaluating the morphology and preservation of cytological material. Methods: There were used 40 residual samples from bronchial washings in liquid based cytology, after determination of the clinical diagnosis, being made subsequently 40 cellblocks using HistoGel. For each cellblock there was made one histological section for analysis of cell morphology, which was subsequently stained with the routine histological staining. After microscope observation, the morphology was evaluated by 3 experts in the field of pathology, based on the parameters: Cellularity, Preservation and Background. Results: The average final score of 3 evaluators, on a scale of 0 to 100, in assessing the morphology of the 40 samples was 55.6. From the 40 histological sections, 5 of them were considered not viable for evaluation. Conclusions: The results obtained indicate median quality maintenance of morphology. However, it is noted that in only 5 cases it was not possible to determine an evaluation, knowing from the outset that these are residual samples with a very scant cellularity. Thus, it is possible to say that the processing of bronchial washings to cellblock using HistoGel contributes to a concentration of the cytological material, allowing its evaluation and subsequent diagnosis. Additional diagnostic techniques are shown equally viable in these cellblocks.

Methacholine Dose-Response Slopes from Maximal Bronchial Challenge Tests in Asthmatic Children: Methodological Aspects

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholin(dose range: 0.097–30.08 umol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a FEV1 ù 20%; and (2) a MFEV1 ù 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % FEV1 × umol−1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student’s t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 ± 2.7 FEV1% z umol−1)was 2.88 times higher than DRR50% (31.6 ± 3.4 DFEV1% z umol−1), and the LSS20% (89.1 ± 2.8% FEV1 z umol−1) was 3.10 times higher than LSS 50% (28.8 ± 1.5%FEV1 z umol−1). The goodness of fit of LSS 50% was significant in all cases, whereas LSS 20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.

Bronchial Asthma in Children: Clinical and Epidemiologic Approach in Different Portuguese Speaking Countries

BACKGROUND: Geographical differences in asthma prevalence are currently accepted, but evidence is sparse due to the lack of multicentre studies using the same protocol. OBJECTIVES: To compare the prevalence of asthma and atopy among schoolchildren from Portuguese speaking countries (ISAAC and Portuguese Study) and evaluate some environmental variables, such as house dust mite exposure. MATERIAL AND METHODS: Significant random samples of schoolchildren studied with standard validated methods--questionnaires, skin prick tests, methacholine bronchial challenge tests; dust bed sampling for analysis of mite antigens. RESULTS: In the ISAAC study, in the 13-14 year-old age group, statistical significant differences were found, with higher wheezing prevalence in Brazil than in Portugal (two-fold). In the Portuguese Study, atopy prevalence ranged between 6.0 and 11.9% in Sal and S. Vicente (Cape Verde), up to 48.6 and 54.1% in Macau and Madeira. Active asthma had the higher values in Madeira (14.6%), and the lower in Macau (1.3%). Cape Verde had intermediate asthma prevalence (10.6 and 7.0%). The bronchial challenge test was positive in 25, 66 and 70% of asthmatic children from Sal, S. Vicente and Madeira respectively. Significant HDM antigen concentrations (Der p1) were found in Cape Verde and Madeira. CONCLUSIONS: There are significant variations in asthma and atopy prevalence between these pediatric populations. The reasons remain under discussion, but genetics linked to race, seem to play a central role, modulated by environmental and lifestyle variables.