Does Bronchial Hyperresponsiveness in Asthma Matter?

Methacholine Challenge Methods

A rationale for the use of nedocromil sodium in the treatment of asthma

Bronchial Hyperresponsiveness in the Assessment of Asthma Control: Airway Hyperresponsiveness in Asthma: Its Measurement and Clinical Significance

Bronchial hyperresponsiveness to methacholine and adenosine monophosphate and the degree of atopy in children with allergic rhinitis

To quantitatively analyze the effects of direct and indirect stimuli on the contraction of gastrocnemius in vivo and in vitro specimen by self-programming. All specimens were divided into four groups: indirect stimuli on specimen in vivo group (n=12), direct stimuli on specimen in vivo group (n=8), indirect stimuli on specimen in vitro group (n=12), direct stimuli on specimen in vitro group (n=8). Indirect stimuli (via sciatic nerve) and direct stimuli (acupuncture needle piercing into gastrocnemius) (stimuli starting from 0 V, cycle 3 s, increment 0.02 V, 150 times) were acted on in vivo and in vitro sciatic nerve gastrocnemius muscle specimen respectively. The effects of electric intensity on the contraction of gastrocnemius were recorded by the experimental system of BL-420F. The data were processed and analyzed by the help of self-programming, to quantitatively obtain key parameters for a single contraction. ① For in vivo specimen, compared with direct stimuli, effects of indirect stimuli were as follows: the threshold intensity, half-intensity and maximal intensity of the specimen were smaller (P＜0.05); the amplitude was larger, the contraction period was longer, and the rising slope was smaller (P＜0.05). ②For in vitro specimen, compared with direct stimuli, effects of indirect stimuli were as follows: the threshold intensity, half-intensity and maximal intensity of indirect stimuli were smaller (P＜0.05); the amplitude was larger, the contraction period was longer, and the rising slope was smaller (P＜0.05). ③Compared with in vitro specimen, there was no significant difference among all the above parameters of in vivo specimen, with either direct or indirect stimuli (P＞0.05). There is no significant difference in the features of single contraction between in vivo and in vitro specimen with either direct or indirect stimuli. However, indirect stimuli can trigger gastrocnemius to produce single contraction more easily than direct stimuli, and the amplitude is larger than that of direct stimuli.

<b>Background:</b> There is increasing evidence of an association between organ specific autoimmune diseases, particularly autoimmune thyroid disease and respiratory morbidity. A study was undertaken to determine whether patients with autoimmune thyroid disease have objective evidence of airway inflammation and dysfunction. <b>Methods:</b> Twenty six non-smoking women with treated hypothyroidism and 19 non-smoking controls completed a symptom questionnaire and underwent full lung function tests, capsaicin cough reflex sensitivity measurement, methacholine challenge test, and sputum induction over two visits. <b>Results:</b> Symptoms of cough (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p = 0.04) were reported more commonly in patients than controls. Patients with hypothyroidism had heightened cough reflex sensitivity compared with controls (geometric mean concentration of capsaicin causing five coughs: 40 <i>v</i> 108 mmol/l; mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to 2.5; p = 0.008) and a significantly higher proportion of patients had airway hyperresponsiveness (methacholine provocative concentration (PC₂₀) &lt;8 mg/ml: 38% <i>v</i> 0%; p = 0.016). Patients with hypothyroidism also had a significantly higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p = 0.048). <b>Conclusion:</b> Patients with treated hypothyroidism report more respiratory symptoms and have objective evidence of airway dysfunction and inflammation.

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Airway hyperresponsiveness to a wide variety of bronchoconstrictor agonists is a characteristic finding in patients with current, symptomatic asthma. The agonists include inhaled pharmacological agonists, such as histamine (1) acting on airway H 1 receptors, the cholinergic agonist methacholine (2) acting on airway M 3 receptors, the cysteinyl-leukotrienes (3) acting on airway Cys-LT 1 receptors, and the stimulatory prostaglandins (PG)D 2 (4) and PGF 2a (5) likely acting on airway TP receptors. These agonists are considered to be direct stimuli causing bronchoconstriction in individuals with asthma, because their action is directly on specific airway receptors. Airway hyperresponsiveness is also present to a number of physical stimuli such as exercise (6), isocapnic hyperventilation of cold, dry air (7), and hypo- and hypertonic aerosols (8). The bronchoconstriction that develops after exposure to the physical stimuli is indirect, because it occurs through the release of constrictor mediators from cells within the airways, which subsequently act on their specific receptors to mediate bronchoconstriction. Another important indirect stimulus for bronchoconstriction in many individuals with asthma is environmental allergens. The responses after inhaled allergens are often quite different from those after the other indirect stimuli, in that the acute bronchoconstrictor responses are often followed by the development of late-phase bronchoconstrictor responses (9), airway inflammation (10), and an increase in airway hyperresponsiveness (11). The focus of this article is to evaluate the evidence that the cysteinyl-leukotrienes (LT) C 4 , D 4 , and E 4 are released in asthmatic airways and are the main cause of bronchoconstriction after exposure to exercise and environmental allergens, and of the changes in airway hyperresponsiveness after the inhalation of allergen.

Bronchial Hyperresponsiveness and Quality of Life in Asthmatics

Kilpeläinen M, Terho EO, Helenius H, Koskenvuo M. Allergy. 2002;57:1130–1135To examine the relationship between childhood farm environments and allergic sensitization and asthma in young adulthood.The 296 participants were Finnish first-year university students (median age, 21.5 years) recruited by questionnaire. One hundred fifty-two subjects (51%) had a history of asthma or wheezing and 144 (49%) had no history of asthma or wheezing.Physicians in both pulmonary and dermatology subspecialties, who were blinded with respect to original questionnaire data concerning prior symptoms and farm environment, conducted baseline examinations. Pulmonary function tests and methacholine challenge tests were performed. Participants were considered to have current asthma if they had experienced clinical symptoms consistent with asthma, such as wheezing, shortness of breath, or cough associated with typical provoking factors, during the preceding 12 months and the results of methacholine challenge or pulmonary function tests were indicative of asthma. Skin prick tests and allergen-specific immunoglobulin E (IgE) tests with multiple indoor, outdoor, food, and latex allergens were performed. Data were analyzed to examine the effects of childhood farm environments on current asthma and allergic sensitization, with adjustment for early childhood pet ownership.Approximately 10% of subjects experienced childhood farm environments at 0 to 6 years of age, and the incidence of current asthma in the total study population was 10.7%. Significantly fewer patients with histories of farm environments had current asthma, compared with nonfarm participants (odds ratio [OR]: 0.22; 95% confidence interval [CI]: 0.07–0.70). No difference in bronchial hyperreactivity or skin test reactivity between groups was seen, although trends in favor of childhood farm environments were observed, with less bronchial hyperreactivity and fewer positive skin test results in this group. Farm environments had a protective effect on cat-specific IgE (OR: 0.10; 95% CI: 0.02–0.47), and participants in this group were more likely to have dust mite-specific IgE (OR: 3.29; 95% CI: 1.21–8.96).Childhood farm environments were protective against asthma in young adulthood. Sensitization to cat allergens was more likely among participants from nonfarm environments, whereas dust mite sensitivity was more common among those from farm environments.Although this study confirms previously described protective effects of farm environments on the development of asthma and allergic sensitization, results should be interpreted cautiously. The number of patients with a history of childhood farm exposure was small, making it difficult to make generalizations about larger populations with similar environmental histories. In addition, the conflicting findings on the protective effects of farm environments against sensitization to cat and dust mite allergens warrant more investigation.

Coronavirus disease 2019 (COVID-19) has a considerable impact on the global healthcare system. Individuals who have recovered from COVID often experience chronic respiratory symptoms that affect their daily lives. This study aimed to assess respiratory dynamics such as airway hyperresponsiveness (AHR) and bronchodilator response in post-COVID patients. This study included 282 adults with respiratory symptoms who underwent provocation tests. The demographic details, clinical symptoms and medical histories were recorded. Baseline spirometry, methacholine challenge tests (MCT) and post-bronchodilator spirometry were performed. Patients were divided into the following four groups: Group 1: non-COVID-19 and negative MCT; Group 2: post-COVID-19 and negative MCT; Group 3: non-COVID-19 and positive MCT; and Group 4: post-COVID-19 and positive MCT. Most post-COVID-19 patients (43.7%) experienced AHR, and wheezing was more common. Patients in Group 4 exhibited increased intensities of dyspnoea, cough and wheezing with the lowest pulmonary function test (PFT) parameters at baseline. Moreover, significant decreases in PFT parameters after the MCT were observed in these patients. Although the prevalence of a low forced expiratory volume in 1 s to forced vital capacity ratio (<70%) was initially 2% in Group 4, it increased to 29% after MCT. No significant differences in allergic history or underlying diseases were observed between the groups. These findings provide comprehensive insights into the AHR and respiratory symptoms of post-COVID-19 individuals, highlighting the characteristics and potential exacerbations in patients with positive MCT results. This emphasises the need of MCT to address respiratory dynamics in post-COVID-19 individuals.

Severe asthma: a consequence of over exuberant repair?

The beta2-adrenoceptor exhibits genetic polymorphism which may be clinically relevant in terms of treatment response or bronchial hyper-responsiveness (BHR). The combined effect of these genotypes, or the haplotype, has not been fully characterized in terms of BHR. We performed a retrospective analysis of the effects of haplotypes of amino acid substitution at position 16 (Gly/Arg) and position 27 (Gln/Glu) on spirometry and BHR to methacholine and adenosine monophosphate (AMP) in 594 asthmatic patients. There was a significant (P < 0.05) overall effect for forced expiratory volume (FEV(1)) but not after correction for steroid dose and atopic status. There were no significant differences for BHR to methacholine or AMP between the different haplotypes and no difference between the numbers of patients with or without clinically relevant BHR. Methacholine PD20 geometric mean-fold difference was 1.63 (95% CI: 0.95-2.80) between Arg-Arg/Gln-Gln and Gly-Gly/Gln-Gln and 1.26 (95% CI: 0.75-2.11) between Gly-Gly/Gln-Gln and Gly-Gly/Glu-Glu. The degree of BHR to indirect and direct stimuli does not differ between beta2-adrenoceptor haplotypes, and haplotypes cannot be used to predict BHR in patients presenting with asthma. Although beta2-adrenoceptor haplotypes do not predict BHR they may be important in predicting response to bronchodilator therapy.

Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.

β2-Agonists: Déjà vu All Over Again: The Second-Generation Controversy