Pulmonology approach in the investigation of chronic unexplained dyspnea / Abordagem pneumológica na investigação de dispneia crônica inexplicada

ABSTRACT Chronic unexplained dyspnea and exercise intolerance represent common, distressing symptoms in outpatients. Clinical history taking and physical examination are the mainstays for diagnostic evaluation. However, the cause of dyspnea may remain elusive even after comprehensive diagnostic evaluation-basic laboratory analyses; chest imaging; pulmonary function testing; and cardiac testing. At that point (and frequently before), patients are usually referred to a pulmonologist, who is expected to be the main physician to solve this conundrum. In this context, cardiopulmonary exercise testing (CPET), to assess physiological and sensory responses from rest to peak exercise, provides a unique opportunity to unmask the mechanisms of the underlying dyspnea and their interactions with a broad spectrum of disorders. However, CPET is underused in clinical practice, possibly due to operational issues (equipment costs, limited availability, and poor remuneration) and limited medical education regarding the method. To counter the latter shortcoming, we aspire to provide a pragmatic strategy for interpreting CPET results. Clustering findings of exercise response allows the characterization of patterns that permit the clinician to narrow the list of possible diagnoses rather than pinpointing a specific etiology. We present a proposal for a diagnostic workup and some illustrative cases assessed by CPET. Given that airway hyperresponsiveness and pulmonary vascular disorders, which are within the purview of pulmonology, are common causes of chronic unexplained dyspnea, we also aim to describe the role of bronchial challenge tests and the diagnostic reasoning for investigating the pulmonary circulation in this context.

RESUMO A dispneia crônica inexplicada e a intolerância ao exercício representam sintomas comuns e angustiantes em pacientes ambulatoriais. O histórico clínico e o exame físico são as bases da avaliação diagnóstica. No entanto, a causa da dispneia pode permanecer inexplicada mesmo após uma avaliação diagnóstica abrangente - análises laboratoriais básicas, exames de imagem do tórax, testes de função pulmonar e testes cardíacos. Nesse momento (e frequentemente antes), os pacientes geralmente são encaminhados a um pneumologista, o qual se espera que seja o principal médico para a resolução desse enigma. Nesse contexto, o teste de exercício cardiopulmonar (TECP), para avaliação de respostas fisiológicas e sensoriais do repouso ao pico do exercício, proporciona uma oportunidade única de desvendar os mecanismos subjacentes à dispneia e as interações desses mecanismos com um amplo espectro de distúrbios. No entanto, o TECP é subutilizado na prática clínica, possivelmente por questões operacionais (custos dos equipamentos, disponibilidade limitada e baixa remuneração) e limitação da formação médica em relação ao método. Para enfrentar esta última deficiência, almejamos fornecer uma estratégia pragmática para a interpretação dos resultados do TECP. O agrupamento dos achados da resposta ao exercício permite a caracterização de padrões que possibilitam ao clínico restringir a lista de possíveis diagnósticos, em vez de apontar uma etiologia específica. Apresentamos uma proposta de avaliação diagnóstica e alguns casos ilustrativos avaliados por TECP. Como a hiper-responsividade das vias aéreas e os distúrbios vasculares pulmonares, que são da competência da pneumologia, são causas comuns de dispneia crônica inexplicada, também objetivamos descrever o papel dos testes de broncoprovocação e o raciocínio diagnóstico para a investigação da circulação pulmonar nesse contexto.

Work-related asthma / Asma relacionada ao trabalho

ABSTRACT Work-related asthma (WRA) is highly prevalent in the adult population. WRA includes occupational asthma (OA), which is asthma caused by workplace exposures, and work-exacerbated asthma (WEA), also known as work-aggravated asthma, which is preexisting or concurrent asthma worsened by workplace conditions. In adults, the estimated prevalence of OA is 16.0%, whereas that of WEA is 21.5%. An increasing number of chemicals used in industrial production, households, and services are associated with the incidence of adult-onset asthma attributable to exposure to chemicals. This review article summarizes the different types of WRA and describes diagnostic procedures, treatment, prevention, and approaches to patient management. It is not always easy to distinguish between OA and WEA. It is important to establish a diagnosis (of sensitizer-/irritant-induced OA or WEA) in order to prevent worsening of symptoms, as well as to prevent other workers from being exposed, by providing early treatment and counseling on social security and work-related issues.

RESUMO A asma relacionada ao trabalho (ART) é um acometimento com elevada prevalência na população adulta. A ART inclui a asma ocupacional (AO), desencadeada pela exposição a um agente presente em um determinado ambiente de trabalho, e a asma agravada ou exacerbada pelo trabalho (AA/ET), que acomete indivíduos com antecedentes de asma ou que iniciaram um quadro de asma concomitante, mas sem relação causal com o ambiente de trabalho. Estima-se que 16,0% e 21,5% da asma no adulto sejam AO e AA/ET, respectivamente. O elevado e crescente número de substâncias químicas usadas na produção industrial, no uso domiciliar ou em serviços é responsável pela incidência de asma associada à exposição a agentes químicos na vida adulta. Este artigo de revisão descreve os principais tipos de ART, os procedimentos para seu diagnóstico, tratamento e prevenção e as condutas frente ao diagnóstico. Nem sempre é fácil a distinção entre AO e AA/ET. A importância do diagnóstico (AO ou AA/ET e asma induzida por sensibilizantes ou irritantes) tem relação com a adoção de medidas de prevenção para evitar que novos indivíduos sejam expostos e que os acometidos apresentem agravamento da doença, utilizando tratamento precoce e fornecendo orientação sobre aspectos previdenciários e trabalhistas.

The KAAACI Standardization Committee Report on the procedure and application of the bronchial provocation tests

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.

Comparison on the profiles of a modified Borg scale and the pediatric dyspnea scale during an induced bronchoconstriction in children with clinical asthma

PURPOSE: Dyspnea is the cardinal symptom of asthma, but it is difficult to quantify clinically. Although modified Borg (mBorg) scale has been successfully used in adult, but there has been some difficulties to apply in children. Recently, Pediatric Dyspnea Scale (PDS) was adequately designed and has been widely used. The aim of this study is to compare 2 evaluating scales of dyspnea provoked by induced-bronchoconstriction in childhood asthma. METHODS: Seventy-three clinically suspected children with asthma were enrolled in this study. Each ‘fractional exhaled nitric oxide (FeNO)’ was documented. Forced expiratory volume in 1 second (FEV₁), mBorg score and PDS score were recorded during methacholine provocation test. RESULTS: Mapping using canonical plot demonstrated global similarity between 2 scales with some distinctive features. Whereas mBorg score showed more diverse categories in low level of dyspnea, PDS score did in medium level of it. A distribution of dyspnea perception score at a 20% decrease in FEV₁ relative to baseline (PS₂₀), a perception score of dyspnea at 20% fall in FEV1 of 2 scales represented similar wide, biphasic feature. Statistical relevance was verified with spearman correlation (R(s)=0.903, P<0.001) and Bland-Altman analysis. PS₂₀ of both scores and FeNO had no statistical relationship. While relationship between PS20 by mBorg score and the concentration of methacholine at 20% fall in FEV₁ (PC₂₀) was not significant (R(s)=0.224, P=0.154), that between PS₂₀ by PDS and PC₂₀ was weak positive (R(s)=0.29, P=0.063). CONCLUSION: PDS had similar pattern to assess the dyspnea with the mBorg scale suggesting adequacy of PDS in evaluating pediatric clinical asthma. We expect these scales to help clinical practice in complementary ways.

Nonspecific Bronchoprovocation Test / 결핵및호흡기질환

Bronchial asthma is a disease characterized by the condition of airway hyper-responsiveness, which serves to produce narrowing of the airway secondary to airway inflammation and/or various spasm-inducing stimulus. Nonspecific bronchoprovocation testing is an important method implemented for the purpose of diagnosing asthma; this test measures the actual degree of airway hyper-responsiveness and utilizes direct and indirect bronchoprovocation testing. Direct bronchoprovocation testing using methacholine or histamine may have superior sensitivity as these substances directly stimulate the airway smooth muscle cells. On the other hand, this method also engenders the specific disadvantage of relatively low specificity. Indirect bronchoprovocation testing using mannitol, exercise, hypertonic saline, adenosine and hyperventilation serves to produce reactions in the airway smooth muscle cells by liberating mediators with stimulation of airway inflammatory cells. Therefore, this method has the advantage of high specificity and also demonstrates relatively low sensitivity. Direct and indirect testing both call for very precise descriptions of very specific measurement conditions. In addition, it has become evident that challenge testing utilizing each of the various bronchoconstrictor stimuli requires distinct and specific protocols. It is therefore important that the clinician understand the mechanism by which the most commonly used bronchoprovocation testing works. It is important that the clinician understand the mechanism of action in the testing, whether direct stimuli (methacholine) or indirect stimuli (mannitol, exercise) is implemented, when the testing is performed and the results interpreted.

The Lung Function Impairment in Non-Atopic Patients With Chronic Rhinosinusitis and Its Correlation Analysis

OBJECTIVES: Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied. METHODS: One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters. RESULTS: The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P<0.05). On peak expiratory flow, there was no difference between three groups. In CRSwNP group, FEV1 was negatively correlated with peripheral blood eosinophil count (PBEC) and duration of disease (r=–0.348, P=0.013 and r=–0.344, P=0.014, respectively), FEF25-75 negatively with VAS, SNOT-20 (r=–0.490, P=0.028 and r=–0.478, P=0.033, respectively) in CRSsNP group. The incidence of positive bronchial provocation and dilation test was lower in CRSwNP group (10% and 0%, respectively), with both 0% in CRSsNP group. The multiple linear regression analysis indicated that change ratio of FEV1 before and after bronchial provocation or dilation test were correlated with PBEC in CRSwNP group (β=0.403, P=0.006). CONCLUSION: CRS leading to impaired maximum ventilation and small airway is associated with the existence of nasal polyp. Lung function impairments can be reflected by PBEC, duration, VAS, and SNOT-20. In CRSwNP patients, PBEC is independent predictor of FEV₁ change ratio.

The relationship of bronchial provocation tests and the onset of the disease / 中国综合临床

Objective To investigate the correlation between bronchial provocation tests and the onset of the disease.Methods One hundred and seven patients who hospitalized in General Hospital of China Aviation from 2013-2014 were selected as our subjects.They all were with unexplained symptoms such as cough and asthma suppress.All the patients were performed bronchial provocation tests.In accordance with the onset time,patients were divided into acute (＜ 3 weeks),subacute (3-8 weeks) and chronic (＞ 8 weeks) groups.The positive rates of bronchial provocation test of three groups were compared.Results Of all 107 patients,36 patients were positive and 71 were negative in terms of bronchial provocation test.The cases with acute,subacute and chronic disease history were 16,36 and 55 respectively.The positive rate of bronchial provocation tests in different onset were 56.3％ (9/16),36.1％ (13/36),23.6％ (13/55) respectively,and there was statistics significant difference(x2 =6.275,P ＜ 0.05).The positive rate of bronchial provocation tests in acute group was higher than that in chronic group (x2 =6.165,P ＜ 0.05).There was positive correlation between the positive rate of bronchial provocation tests and the onset,and the correlation coefficient Pearson was 0.239 (P ＜0.05).Conclusion There is a correlation between the positive rate of bronchial provocation tests and the onset.We should strengthen the monitoring in patients with acute onset and follow-up.

Respostas fisiológicas em adolescentes obesos submetidos à broncoprovocação com solução salina hipertônica / Physiological responses in obese adolescents submitted to bronchial provocation with hypertonic saline

INTRODUÇÃO: A hiper-responsividade brônquica é a resposta do aumento dos mecanismos fisiológicos protetores das vias aéreas em indivíduos atópicos e não atópicos. Além disso, a magnitude da hiperresponsividade aérea apresenta influência conforme o grau de obesidade. OBJETIVO: Avaliar as respostas fisiológicas em adolescentes obesos submetidos a hiper-responsividade brônquica a solução salina hipertônica. MATERIAIS E MÉTODOS: Estudo descritivo, transversal e correlacional composto por 15 adolescentes obesos, de ambos os gêneros. O diagnóstico de asma foi realizado por meio de histórico clínico e questionário ISAAC, e a obesidade pelo IMC acima do percentil 95. Utilizou-se o teste de broncoprovocação por solução salina hipertônica para avaliação da hiper-responsividade brônquica, considerando positiva uma diminuição do volume expiratório forçado no primeiro segundo (VEF1) > 15% do valor pré-solução salina e a intensidade da hiper-responsividade brônquica foi calculada pela queda percentual máxima do VEF1 (% Queda máxVEF1). Foram utilizados o teste t independente ou U de Mann-Whitney e a correlação de Spearman rho (p < 0,05). RESULTADOS: Não foram encontradas diferenças significativas entre os asmáticos e não asmáticos para as variáveis antropométricas, espirométricas, lipídicas e hemodinâmicas. Verificaram-se moderadas correlações positivas e diferenças significativas entre o % Queda máxVEF1 com o IMC (p = 0,040) e IMC escore-Z (p = 0,028). Foram detectadas correlações negativas e diferenças significativas para a Queda máxVEF1 e leucócitos (p = 0,005) e para o % Queda máxVEF1 com o sulfato de dehidropiandrosterona (p = 0,032). CONCLUSÃO: Pode-se concluir que os adolescentes obesos submetidos a hiper-responsividade brônquica apresentam alterações espirométricas que estão associadas às inflamações sistêmicas da obesidade.

INTRODUCTION: The bronchial hyperresponsiveness is the response of increased physiological protective mechanisms in the airways of atopic and non-atopic individuals. Furthermore, the magnitude of hyperresponsiveness influences provider submits with the degree of obesity. OBJECTIVE: To evaluate the physiological responses in obese adolescents undergoing bronchial hyperresponsiveness to hypertonic saline. MATERIALS AND METHODS: Cross-sectional and correlation study consisted of 15 obese adolescents of both genders. The diagnosis of asthma was made by clinical history and ISAAC, and obesity as BMI above 95th percentile. We used the bronchial provocation test by hypertonic saline for the assessment of bronchial hyperresponsiveness, considering positive a decrease in forced expiratory volume in one second (FEV1) > 15% of pre-saline and the intensity of bronchial hyperresponsiveness was calculated as the percentage fall maximum of FEV1 (% Fall máxFEV1). We used the independent T or Mann-Whitney U test and Spearman's rho correlation (p < 0.05). RESULTS: There were no significant differences between asthmatics and non-asthmatics for anthropometric, spirometric, lipid and hemodynamic variables. There were positive correlations and significant differences between the % Fall máxFEV1 with BMI (p = 0.040) and BMI Z-score (p = 0.028). There were detected negative correlations with significant differences for Fall máxFEV1 and leukocytes (p = 0.005) and the % Fall máxFEV1 with dehydropiandrosterone sulfate (p = 0.032). CONCLUSION: It can be concluded that obese adolescents have bronchial hyperresponsiveness presented spirometric changes that are associated with systemic inflammation of obesity.

Is It Necessary to Re-Evaluate Airway Hyperresponsiveness During Treatment of Mild Asthma? / 대한내과학회지

BACKGROUND/AIMS: Airway hyperresponsiveness (AHR) is one of the typical characteristics of asthma. However, its natural course is unknown. The presence of AHR is often not assessed in asthmatics undergoing medical treatment. We investigated the changes of AHR as compared with clinical parameters in patients with mild asthma. METHODS: We enrolled patients who were diagnosed with asthma, but were asymptomatic for > 3 months while undergoing medical treatment. AHR was measured using a methacholine bronchial provocation test after a 2-week washout period. AHR-negativity was defined as a PC20 > 25 mg/mL. Clinical parameters were retrospectively compared between the AHR-negative and -positive patients. RESULTS: Among 54 patients, 22 (40.7%) were AHR negative. Factors associated with the maintenance of AHR were male sex, presence of dyspnea, and high-dose inhaled corticosteroid plus long-acting beta agonists at initial presentation (respectively, p < 0.05). Age, symptoms other than dyspnea, blood tests, results of spirometry, diagnostic methods at presentation, and time from diagnosis to follow-up testing were not significantly different between AHR-negative and AHR-positive patients. Multivariate analyses failed to show a significant difference between the two groups, except for male sex (p = 0.014). CONCLUSIONS: Approximately 40% of patients with mild asthma show no AHR or clinical remission of the disease. Male sex may be a predictive factor for persistent AHR. However, altered AHR status is not predictable in patients with mild asthma undergoing medical treatment. Therefore, the cessation of regular controller might be advocated, and reassessment of AHR should be mandatory.

Implement bronchial provocative tests in children with asthma remission / 国际儿科学杂志

Bronchial asthma is one of the most common children health problems, with still increasing prevalence.Bronchial hyperresponsiveness is a characteristic feature of asthma,and its measurement may provide a useful adjunct in the diagnosis of asthma. Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness persists in approximately one half of these subjects, so implement the bronchial provocative tests in children with asthma remission may appears very important.

The clinical value of changes in small airway function in patients with chronic cough / 中国医师进修杂志

Objective To evaluate the clinical value of small airway function indexes in lung function in the differential diagnosis of patients with chronic cough. Methods One hundred and nine patients with chronic cough were managed with conventional pulmonary function testing and bronchial provocation test. The difference of small airway function between bronchial provocation test positive and negative indicators, and the difference of lung function and the positive rate of bronchial provocation test between small airway dysfunction and normal small airway function was observed. Results Sixty cases in 109 patients had positive bronchial provocation test and 49 eases were negative. Peak expiratory flow (PEF),maximal midexpiratory flow rate (MMEF)75/25, forced expiratory flow of vital capacity (FEF)25, FEF50,FEF75 were lower than those in negative eases (P<0.05 ), ventilatory capacity, forced vital capacity( FVC ),forced expiratory volume in one second (FEV_1, FEV_1/FVC had no significant differences. Forty-eight eases had small airway dysfunction. There were 39 cases with positive bronchial provocation test, and the positiverate was 81.2%. In 61 cases without small airway function, there were 21 cases with positive bronchial provocation test(34.4%). There was significant difference in positive rate of bronchial provocation test between them (P <0.01). Conclusions Small airway function indexes in lung function can predict airway hyperresponsiveness. In a large number of primary hospital where bronchial provocation test can not carry out,it helps to identify patients with early cough variance asthma. In particular, it is more important in young patients with small airway disease.

The predicting value of small airway diseases for asthma in patients with chronic cough / 中国实用内科杂志

Objective The aim of this study is to investigate the correlation between small airway disease and airway hyper-responsiveness,and explore the predicting value of small airway diseases for asthma.Methods Pulmonary function tests and bronchial provocation tests were performed in 249 patients with chronic cough from Sep. 2004 to Sep. 2006.The incidence of small airway disease and airway hyper-responsiveness were observed.Results There were 91 patients with small airway disease,and 103 patients with positive tests for bronchial provocation in total 249 chronic cough patients.The incidence of positive tests for bronchial provocation in 91 patients(73.63%)with small airway disease was significantly higher than that in 158 patients(22.78%)without it,P

Diagnostic Value of Bronchial Hyperreactivity Using Chest Auscultation and Oxygen Saturation Measurement in Preschool Children with a History of Wheezing / 소아알레르기및호흡기학회지

PURPOSE: This study aimed to evaluate the validity of chest auscultation and oxygen saturation measurement in the assessment of bronchial hyperreactivity to inhaled methacholine in preschool children who were thought to be asthmatic clinically. METHODS: Seventy-two children with a history of more than three wheezing episodes in the previous year were considered the asthma group and underwent methacholine bronchial challenges. Provocation concentration at wheezing (PCw), at 5% fall of oxygen saturation (PCSat), and at 50% increase in respiratory rate (PCRR) were determined in each subject. One hundred and eighteen children who have had less than two wheezing episodes in their life served as control group. RESULTS: The geometric means of PCw, PCSat, and PCRR of asthma group were significantly lower than those of the control group. The optimal cut-off level for PCw was 8 mg/mL, giving a sensitivity of 63% and a specificity of 78%. Corresponding values for PCSat and PCRR were 8 mg/mL (72%, 67%) and 16 mg/mL (49%, 86%), respectively. The area under the receiver operating characteristic (ROC) curve for PCw, PCSat, and PCRR were 0.80, 0.88, and 0.70 respectively. The discriminative capacity of PCSat as judged by ROC curve analysis exceed those of PCw and PCRR. CONCLUSION: These findings provide support for the use of chest auscultation and oxygen saturation measurement as a tool in the assessment of bronchial hyperreactivity. The cut-off level of 8 mg/mL for PCSat, owing to its highest discriminative capacity, may be useful for the diagnosis of asthma in preschool children.

Oropharyngeal Angioedema Induced by Inhaled Histamine

Inhaled histamine used to measure airway responsiveness produces some side effects more frequently than does methacholine. It is possible that the inhaled histamine induces the side effects in asthmatics with increased end organ responsiveness to histamine. A 56-yr-old woman with chronic idiopathic angioedema presented with asthma-like symptoms. Methacholine challenge test was performed, with a negative result. Five days later, histamine inhalation test was done. FEV1 fell by 37% after inhalation of histamine concentration of 8 mg/mL. Immediately thereafter, severe angioedema on face, lips, and oropharyngeal area, foreign body sensation at throat, and hoarseness occurred. To assess end organ responsiveness to histamine, skin prick tests with doubling concentrations of histamine (0.03-16 mg/mL) were carried out on the forearm of the patient and six age- and sex-matched asthmatic controls. The wheal areas were measured. The patient showed greater skin responses than the controls. Regression analysis showed that the intercept and slope were greater than cut-off levels determined from six controls. The patient showed an increased skin wheal response to histamine, indicating the enhanced end organ responsiveness to histamine, which is likely to contribute to the development of the oropharyngeal angioedema by inhaled histamine.

The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in bronchial asthma and allergic rhinitis

Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness, but results at the moment are less than convincing. The present study was conducted to evaluate the effect of immunotherapy on the degree of nonspecific bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA) and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test, allergic skin test, serum IgE and peripheral blood eosinophil counts were performed before and after 12 months or more of immunotherapy. The improved group, as determined by a shift of at least two doubling concentrations of methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR (n=13). The geometric mean of the methacholine provocational concentration (PC20) changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In conclusion, nonspecific bronchial hyperresponsiveness was improved by immunotherapy in three quarters of the allergic rhinitis cases and in about a half of the allergic bronchial asthma patients, which suggests that immunotherapy might be helpful at preventing the development of bronchial hyperresponsiveness in allergic rhinitis patients, and that it does not improve bronchial hyperresponsiveness in about a half of allergic bronchial asthma patients.