Airway Responsiveness In Patients Research Articles

Effect of Biologic Therapies on Airway Hyperresponsiveness and Allergic Response: A Systematic Literature Review.

Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma. We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma. Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified. Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.

Changes of the airway reactivity in patients with rhinosinusitis

Abstract Rhinosinusitis is one of the most common conditions in primary and secondary care all over the world. Rhinosinusitis together with asthma and gastroesophageal reflux disease represent the most common causes of chronic cough. The relationship between rhinosinusitis and cough is still not completely understood, however, direct stimulation of nasal mucosa, upper airway cough syndrome, inflammation of the airways, and cough reflex sensitisation play the crucial role in the pathogenesis of chronic cough.

DM-induced Hypermethylation of IR and IGF1R attenuates mast cell activation and airway responsiveness in rats.

Diabetes has been reported to modulate the airway smooth muscle reactivity and lead to attenuation of allergic inflammatory response in the lungs. In this study, we aimed to study the effect of insulin on cell activation and airway responsiveness in patients with diabetes mellitus (DM). The airway contraction in rat model groups including a non‐DM group, a non‐DM+INDUCTION group, a DM+INDUCTION group and a DM+INDUCTION+INSULIN group was measured to observe the effect of insulin on airway responsiveness. Radioenzymatic assay was conducted to measure the levels of histamine, and ELISA assay was conducted to measure bronchial levels of interleukin (IL)‐1b, tumour necrosis factor (TNF)‐a, cytokine‐induced neutrophil chemoattractant (CINC)‐1, P‐selectin and β‐hexosaminidase. The tension in the main and intrapulmonary bronchi of DM+INDUCTION rats was lower than that of the non‐DM+INDUCTION rats, whereas the treatment of insulin partly restored the normal airway responsiveness to OA in DM rats. The release of histamine was remarkably suppressed in DM+INDUCTION rats but was recovered by the insulin treatment. Also, OA significantly increased the levels of IL‐1b, TNF‐a, CINC‐1 and P‐selectin in non‐DM rats, whereas insulin treatment in DM+INDUCTION rats partly restored the normal levels of IL‐1b, TNF‐a, CINC‐1 and P‐selectin in DM rats. Moreover, the expression of IR and IGF1R was evidently suppressed in DM rats, with the methylation of both IR and IGF1R promoters was aggravated in DM rats. Therefore, we demonstrated that DM‐induced hypermethylation inhibited mast cell activation and airway responsiveness, which could be reversed by insulin treatment.

Usefulness of mannitol challenge testing for diagnosing asthma in everyday clinical practice

Background: The mannitol test is widely used for assessment of airway responsiveness in patients with possible asthma, but our knowledge of the value in everyday clinical practice is limited.Objective: To investigate the diagnostic value of the mannitol test in a clinical setting.Methods: All patients having a mannitol challenge test as part of their diagnostic work-up for asthma at the respiratory outpatient clinic, Hvidovre Hospital, over a 5-year period were included in the present analysis. Case history, including previous diagnoses, spirometry, exhaled nitric oxide (FENO) was obtained. The mannitol challenge was performed according to guidelines, i.e. increasing doses of mannitol (from 5 to 635 mg) until maximum dose or a 15% decline in FEV1 (PD15) was achieved (positive test defined as a PD15 < 635 mg).Results: Our cohort comprised 566 patients (210 men). Post-challenge, 247 patients were diagnosed with asthma by a specialist in respiratory medicine, of whom 138 (56%) had a positive mannitol test. A diagnosis of asthma was ruled out by the specialist in 319 individuals, of whom 18 (6%) had a positive mannitol test and 77 (24%) previous doctor-diagnosed asthma (but with no evidence of a confirmatory test). The specificity and sensitivity of the test was 94% and 56%, respectively. Female gender (p = 0.005), increasing BMI (p < 0.001), exercise-induced cough (p = 0.002), night-time respiratory symptoms (p = 0.002), low FEV1/FVC ratio (p = 0.008) and high FENO (p < 0.001) were determinants for a positive mannitol test.Conclusion: In everyday clinical work-up of patients with possible asthma, the sensitivity and specificity of the mannitol challenge test is comparable to previous controlled trials.

Comparison of the effects of esomeprazole and fundoplication on airway responsiveness in patients with gastro‐oesophageal reflux disease

Gastro-oesophageal reflux disease (GORD) is suggested to cause or aggravate several respiratory conditions. Studies with proton pump inhibitors have resulted in only minor improvements in pulmonary outcomes in patients with GORD. It has been speculated that operative treatment of GORD might be more efficient as it also diminishes non-acidic reflux. To compare the effects of esomeprazole 40 mg bid and fundoplication on airway responsiveness, forced expiratory volume in 1 s (FEV1), exhaled nitric oxide (NO) and respiratory symptoms in patients with moderate-to-severe GORD. Sixty-nine GORD patients had methacholine inhalation challenge performed on them, and FEV1, exhaled NO and respiratory symptoms were measured at baseline, after a 3-month treatment with esomeprazole and 3 months after fundoplication. Primary outcome variable was dose-response slope (DRS), i.e. decline in FEV1 during methacholine challenge divided with the amount of methacholine administered (%/μmol). Pre-defined subgroup analysis was performed among those with concomitant asthma (n = 12). There was no improvement in DRS, FEV1 or exhaled NO after esomeprazole treatment or fundoplication. Cough and dyspnoea measured with visual analog scale improved with esomeprazole treatment (P < 0.001), and further after fundoplication (P < 0.001). Among those with concomitant asthma, significant improvements in St George Respiratory Questionnaire (SGRQ) scores could be seen after fundoplication. Neither esomeprazole treatment nor fundoplication diminishes airway responsiveness or exhaled NO, or improves FEV1 in patients with GORD. Improvements in respiratory symptoms and SGRQ scores after GORD treatments could be detected. However, as this was not a placebo-controlled study, the findings in these secondary endpoints should not be emphasised. ClinicalTrials.cov: NCT00994708.

Effects of obesity and weight loss on airway physiology and inflammation in asthma

Obesity is a major risk factor for asthma, but the mechanisms for the development of asthma in the setting of obesity are not known. The purpose of this article is to review the effects of obesity on airway inflammation in patients with asthma, and to discuss the effects of obesity on airway reactivity in patients with asthma.Obesity is particularly a risk factor for non-atopic asthma. Airway eosinophilic inflammation is not increased in obesity, in fact the preponderance of the evidence suggests that airway eosinophilia is decreased in obesity. There is some preliminary data suggesting that airway neutrophilia may be increased in obesity, and that this may be particularly related to dietary fats. Obesity also alters adaptive immunity, and may suppress lymphocyte function typically associated with asthmatic airway inflammation.Population based studies are somewhat inconsistent on the relationship between airway reactivity and asthma, however, recent studies in bariatric surgery show that weight loss surgery in severely obese patients decreases airway reactivity. One study suggested that this was particularly the case for those with low IgE (a marker of a low TH2 asthma phenotype), suggesting there may be some heterogeneity in asthma in obesity.There are likely to be two phenotypes of asthma in the obese: one group with early onset disease and asthma complicated by obesity, and a 2nd group with late onset disease with asthma consequent to obesity. Obesity leads to profound changes in airway function, and adaptive and innate immune responses which alter the nature of pre-existing allergic airway disease, and also cause new onset asthmatic disease.

Effect of Obesity on Asthma Phenotype is Dependent upon Asthma Severity

Background. We recently reported that obese and non-obese patients with asthma have similar airflow limitation and bronchodilator responsiveness, but obese patients have more symptoms overall. There is limited information on the effect of obesity on asthmatics of varying severity measured by objective physiological parameters. Understanding how obesity affects asthmatics of differing severity can provide insights into the pathogenesis of asthma in the obese and a rationale for the therapeutic approach to such patients. Methods. Participants with asthma from two American Lung Association—Asthma Clinical Research Center (ALA-ACRC) studies were grouped by tertiles of airflow obstruction (forced expiratory volume in one second (FEV1%) predicted, FEV1/forced vital capacity (FVC)) and methacholine reactivity (PC20FEV1). Within each tertile, we examined the independent effect of body mass index (BMI), divided into normal weight, overweight, and obese categories, on lung function, airway reactivity, and symptoms. Results. Overall, both FEV1 and FVC decreased and symptoms worsened with increasing BMI; airway reactivity was unchanged. When stratified by the degree of airflow obstruction, higher BMI was not associated with greater airway reactivity to methacholine. Higher BMI was associated with more asthma symptoms only in the least obstructed FEV1/FVC tertile. When stratified by degree of airway reactivity, BMI was inversely associated with FVC in all PC20FEV1 tertiles. BMI was directly associated with asthma symptoms only in those with the least airway reactivity. Conclusions. Obesity does not influence airway reactivity in patients with asthma and it is associated with more symptoms only in those with less severe disease.

Airway response to emotional stimuli in asthma: the role of the cholinergic pathway

In asthma, airways constrict in response to emotion and stress, but underlying mechanisms, potential extrathoracic contributions, and associations with airway pathophysiology have not been elucidated. We therefore investigated the role of the cholinergic pathway in emotion-induced airway responses in patients with asthma and the association of these responses with airway pathophysiology. Patients with asthma (n=54) and healthy participants (n=25) received either 40 microg ipratropium bromide or a placebo in a double-blind double-dummy cross-over design in two laboratory sessions with experimental emotion induction. Stimuli were preevaluated films and pictures of pleasant, unpleasant, and neutral quality. Respiratory resistance and reactance at 5 and 20 Hz were measured continuously before and during presentations, together with respiration by impedance plethysmography and end-tidal PCO2 by capnometry. In addition, measures of airway inflammation (fraction of exhaled nitric oxide), airway hyperreactivity (methacholine challenge), and reversibility of obstruction were obtained. Respiratory resistance at 5 and 20 Hz increased during unpleasant stimuli in asthma patients. This response was blocked by ipratropium bromide and was not substantially associated with asthma severity, airway inflammation, hyperreactivity and reversibility, or pattern of ventilation and PCO2. Under the placebo condition, changes in resistance during unpleasant films were positively correlated with patients' reports of psychological asthma triggers. In conclusion, airway constriction to unpleasant stimuli in asthma depends on an intact cholinergic pathway, is largely due to the central airways, and is not substantially associated with other indicators of airway pathology. Its link to the perceived psychological triggers in patients' daily lives suggests a physiological basis for emotion-induced asthma.

Effect of Insulin on Airway Responsiveness in Patients with Type 2 Diabetes Mellitus: A Cohort Study

Background. The correlation between low insulin levels and a decreased sensitivity of the muscarinic receptor has been shown on induced-diabetes animal models. We designed a cohort study with the aim of evaluating the effects of insulin therapy on airway responsiveness (AR) in human patients with type 2 diabetes mellitus. Methods. We enrolled 92 patients with type 2 diabetes who had switched from oral anti-diabetic therapy to treatment by insulin subcutaneous injection. Patients were administered the methacholine challenge test (MCT) at time 0 (pre-insulin therapy) and at intervals of 15, 30, 90, 180, and 360 days after insulin treatment. The decline of forced expiratory volume in 1 second (FEV1)% from baseline (Δ FEV1) in response to inhaled methacholine (MCH) was determined to assess airway hyper-responsiveness (AHR). Results. A total of 81 patients (18 women and 63 men) completed the study. Their mean age was 58 ± 7 years and the mean duration of disease was 13.5 ± 7.7 years. The mean decrease of FEV1 at pre-insulin assessment was 2.96 ± 2.6%. Compared with the pre-insulin value, a significant increase of Δ FEV1 was observed at 15, 30, and 90 days after treatment (6.25%, CI 95% 5.4 to 7.2, p = 0.0005; 7.64%, CI 95% 6.6 to 8.1, p < 0.001; 6.45%, CI 95% 5.5 to 7.3, p = 0.0004, respectively), while after 180 and 360 days AR was similar to pre-insulin values (Δ FEV1, 3.62%, CI 95% 2.7 to 3.5 and 3.11%, CI 95% 7.9 to 9.3, respectively). Conclusions. The finding of an increased AR in patients with type 2 diabetes during the first 3 months of insulin therapy may underline the importance of monitoring pulmonary function and respiratory symptoms in patients switching from oral anti-diabetic drugs to insulin therapy, especially in the subset of individuals with respiratory disorders.

Effects of phenoterol and histamine on lung function in patients with diabetes mellitus

The purpose of the study was to investigate airway reactivity in patients with diabetes mellitus. We examined 68 patients with diabetes mellitus of 16 to 66 years of age. Of them, 29 patients (20 with diabetes mellitus type 1 and 9 with diabetes mellitus type 2) were tested with phenoterol (the 1st group). The 2nd group patients (12 with diabetes mellitus type 1 and 27 with diabetes mellitus type 2) were examined with histamine challenge test. Bronchodilator test (ΔFEV 1 > 200 ml or > 12 % of the baseline value) was positive in 6 (20.7 %) patients, five of them had diabetes type 1. The histamine challenge test was positive in 9 patients with diabetes type 2 (23.1 %). This was an evidence of significant bronchial hyperreactivity. A qualitative analysis using Fisher's discriminant criterion revealed the following correlations: 1) between bronchial hyperreactivity and a type of diabetes mellitus; 2) between bronchial hyperreactivity and administration of oral antidiabetic drugs. Correlations between bronchial hyperreactivity, body mass index, duration of the disease and late complications of diabetes mellitus were not revealed. In conclusion, the positive bronchodilator test predominated in patients with diabetes mellitus type 1 and bronchial hyperreactivity for histamine was mainly detected in patients with diabetes mellitus type 2. This could be considered as an evidence of different mechanisms of bronchoconstriction in patients with diabetes mellitus types 1 and 2. Generally, susceptibility to bronchoconstriction may be an unfavorable factor for occurrence of nonspecific lung disease in patients with diabetes mellitus.

Relationship between coronary spasticity and airway responsiveness in patients with coronary spastic angina

Relationship between coronary spasticity and airway responsiveness in patients with coronary spastic angina

Comparison of ΔFVC between patients with allergic rhinitis with airway hypersensitivity and patients with mild asthma

In asthmatic individuals, airway sensitivity and maximal airway response are increased. Airway sensitivity is usually evaluated by measuring the provocation concentration of inhaled methacholine or histamine that causes a decrease in forced expiratory volume in 1 second of 20% (PC20). The percentage decrease in forced vital capacity at the PC20 (deltaFVC) has been proposed as a surrogate marker for maximal airway response. Individuals with allergic rhinitis and no clinical evidence of asthma frequently exhibit airway hypersensitivity. To compare the deltaFVC between patients with allergic rhinitis and mild asthmatic patients with a similar degree of airway hypersensitivity. A retrospective analysis of methacholine challenge test data from 72 children with allergic rhinitis and airway hypersensitivity (methacholine PC20 < 16 mg/mL) (rhinitis group) and from 72 children with mild atopic asthma matched to the rhinitis group regarding the methacholine PC20 (asthma group). The deltaFVC was calculated on the concentration-response curve to methacholine. The mean +/- SD deltaFVC was significantly lower in the rhinitis group (15.0% +/- 3.6%) vs the asthma group (17.4% +/- 5.3%) (P = .002). There was no significant correlation between the deltaFVC and PC20 in the rhinitis (r = -0.101; P = .41) and asthma (r = -0.023; P = .85) groups when 2 patients with PC20 less than 1 mg/mL were excluded from each group. Patients with allergic rhinitis and airway hypersensitivity had a significantly lower deltaFVC than methacholine PC20-matched mild asthmatic patients, suggesting that the level of maximal airway response in patients with allergic rhinitis is lower than that in mild asthmatic patients with a similar degree of airway hypersensitivity.

Airway Hyperresponsiveness in Patients With Coronary Spastic Angina Relationship Between Coronary Spasticity and Airway Responsiveness

Several reports have suggested a possible link between bronchial asthma and coronary spasm, but the possibility of a relationship in coronary spastic angina (CSA) has not been clarified. Airway responsiveness to methacholine and coronary spasticity to acetylcholine were examined in 42 patients with CSA and 36 patients with chest pain syndrome (CP). Furthermore, 18 control subjects were examined and their airway responsiveness compared with that of the CSA and CP patients. The incidence of airway hyperresponsiveness was significantly higher in the CSA group (74%) than in the CP (19%) and control (17%) groups (p<0.0001). The geometric mean of the log minimum dose (Dmin), defined as the cumulative dose at the point at which respiratory conductance began to decrease, was significantly lower in the CSA group (0.75 log units) than in the CP (1.20 log units) and control (1.38 log units) groups (p=0.004). These results demonstrate that acetylcholine-induced coronary spasticity is significantly related to methacholine-induced airway responsiveness in patients with CSA. A generalized hyperresponsiveness of the vascular and nonvascular smooth muscles, including that through cholinergic mechanisms, may exist in patients with CSA.

Sources de partialite chez les auteurs de guides de pratique clinique

BACKGROUND: Cessation of regular therapy with inhaled beta 2 agonists in patients with asthma may lead to a temporary deterioration of lung function and airway responsiveness. Few such studies have been reported in patients with chronic obstructive pulmonary disease (COPD), so an investigation was carried out to determine whether rebound airway responsiveness and rebound bronchoconstriction also occurs in COPD and if there is any relationship with the dose of beta 2 agonist being used. METHODS: Lung function (forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF)), airway responsiveness (PC20 methacholine (PC20)) and symptoms were assessed in a double blind, placebo controlled crossover study during and after cessation of two weeks regular treatment with placebo, and low dose (250 micrograms) and high dose (1000 micrograms) inhaled terbutaline via a dry powder inhaler (Turbohaler) all given three times a day. Sixteen non-allergic patients with COPD of mean (SD) age 58.7 (6.5) years, FEV1 57.1 (12.8)% of predicted, and reversibility on 1000 micrograms terbutaline of 4.5 (3.5)% predicted were studied. PC20 and FEV1 were measured 10, 14, 34 and 82 hours after the last inhalation of terbutaline or placebo. Measurements performed at 10, 14, and 34 hours were expressed relative to 82 hour values in each period, transformed into an area under the curve (AUC) value and analysed by ANOVA. RESULTS: Mean morning and evening PEF increased during terbutaline treatment. PC20 and FEV1 did not change after cessation of terbutaline treatment. CONCLUSIONS: Cessation of regular treatment with both low and high dose inhaled terbutaline does not result in a rebound bronchoconstriction and rebound airway responsiveness in patients with COPD.

Changes in airway inflammation following nasal allergic challenge in patients with seasonal rhinitis

Seasonal allergic rhinitis could predispose to the development of chronic bronchial inflammation as observed in asthma. However, direct links between nasal inflammation, bronchial inflammation and airway responsiveness in patients with seasonal allergic rhinitis and without asthma are not fully understood. The aim of this study was to analyse the changes induced by allergic nasal challenge outside the pollen season in airway responsiveness and bronchial inflammation of patients with seasonal allergic rhinitis. Nine patients were evaluated after either grass pollens or placebo nasal challenge in a randomized cross-over double-blinded trial. Nasal parameters were recorded hourly and airway responsiveness was assessed by methacholine challenge. Cytological examinations and cytokine measurements were performed in nasal lavage and induced sputum. Eosinophil activation was investigated by eosinophil-cationic protein expression and secretion. Airway responsiveness was increased after allergic nasal challenge. Total eosinophils and eosinophils expressing eosinophil-cationic protein were increased in induced sputum after allergic nasal challenge. Both eosinophil number and eosinophil-cationic protein concentration in induced sputum were correlated to methacholine responsiveness. These results suggest that eosinophils participate to the bronchial inflammation in patients with seasonal allergic rhinitis following allergic nasal challenge outside the pollen season and might explain changes in airway responsiveness.

Effect of Pet Removal on Pet Allergic Asthma

Allergen avoidance has been recommended in the management of allergic asthma. Very few studies have assessed the effect of pet removal on pet allergic asthma. We examined the effect of pet removal from homes on pulmonary function testing, airway hyperresponsiveness, and medication use. Prospective, nonrandomized, nonblinded observational study. Subjects included 20 symptomatic patients with newly diagnosed pet allergic asthma who were keeping domestic animals, including hamsters, cats, dogs, and ferrets, and were sensitized to the animals. They were treated with inhaled corticosteroids or other medications according to recommendations by level of severity of the Global Initiative for Asthma. Methacholine inhalation tests were performed regularly before and after starting medication. Clinical features were compared between the patients who gave away their pets according to recommendations by the clinician (removal group) and the patients who refused to give away their pets (keeping group). There were 10 patients in both the removal group and the keeping group. After >or= 1 year of follow-up with or without pet removal, a 5.9-fold increase in the provocative concentration of methacholine causing a 20% fall in FEV(1) was observed in the removal group compared with a 2.3-fold increase in the keeping group (p = 0.04). There were no significant differences in the changes in FEV(1) and peak flow variability. Finally, no patient received inhaled corticosteroids in the removal group, whereas all but one of the patients needed beclomethasone dipropionate (mean dose, 600 mug/d) in the keeping group. This study indicates that removal of pets from homes reduces airway responsiveness in patients with pet allergic asthma more than optimal pharmacotherapy alone, thereby enabling a decrease in inhaled corticosteroid doses.

Hiperreactividade brônquica na sarcoidose

The purpose of this study was to measure airway responsiveness in patients with sarcoidosis using bronchoprovocation test with methacholine (BPT) in comparison to roentgenographic findings, respiratory symptoms, activity and duration of the disease. There were 17 patients with Sarcoidosis, 20 asthmatics and 21 assymptomatics. We used the tidal breathing method with standardizes output for the nebulizers. We administered increasing and successively concentrations of methacholine beginning with 0.125 to 16mg/ml. The responses were measured by changes in FEV1 or the final concentration was reached. The results were expressed as the concentration of methacholine causing 20% fall in FEV1 (PC20). Aerosolized bronchodilator was given at the completion of all tests. There were 4 patients with sarcoidosis who had positive BPT, 3 of them with PC20<8mg/ml associated with respiratory symptoms, bilateral hilar adenopathy, more than twoyear duration and active disease. All the asthmatic subjects had positive BPT with CP20<8mg/ml. The entire assymptomatic group had negative BPT. Positive bronchodilator response was reached in 6 patients with sarcoidosis, 20 asthmatics and 8 assymptomatic subjects. We concluded that: (a) airway responsiveness can be reached in 17.6% patients with sarcoidosis related to bilateral hilar adenopathy, chronic and active disease; (b) 50% of sarcoidosis patients with cough and/or wheeze had positive BPT, (c) the BPT was able to discriminate asthmatic from assymptomatic subjects.Rev Port Pneumol 2005; XI (2): 97-110

Effects of the alpha2-adrenoceptor agonist dexmedetomidine on bronchoconstriction in dogs.

Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that alpha2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective alpha2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown. After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 microg/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated. At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone). alpha2-Adrenoceptor stimulation with intravenous dexmedetomidine completely blocked histamine-induced bronchoconstriction in dogs. Therefore, dexmedetomidine might be beneficial to decrease airway reactivity in patients with chronic obstructive pulmonary disease or asthma, particularly during weaning from mechanical ventilation, when neurally mediated airway reflexes may be elicited.

Airways reactivity in patients with CF.

Airways reactivity, hyper-reactivity, and hyper-responsiveness are terms used to describe airways for which there appears to be increased bronchial smooth muscle tone or responsiveness. Some patients with cystic fibrosis (CF) have concomitant asthma causing airway hyperresponsiveness as manifested by recurrent acute symptoms of dyspnea that is impressively responsive to an inhaled beta 2 agonist and/or systemic corticosteroids. However, many others have a degree of bronchodilator responsiveness in the absence of an impressive clinical response to such anti-asthmatic treatment. In contrast to those with asthma, exercise does not induce bronchospasm and can even cause bronchodilatation in patients with CF who have bronchodilator responsiveness in the absence of asthma. The airway hyperresponsiveness of CF also differs in its response to histamine induced bronchospasm which is effectively reversed with ipratropium in patients with CF who symptomatically do not have asthma, whereas ipratropium does not adequately reverse histamine-induced bronchospasm in those with concomitant symptoms of asthma. These and other data suggest that the increased airway reactivity in patients with CF is vagally mediated and results from the airway damage caused by the lung disease. The use of bronchodilators as a routine part of CF lung disease care is controversial, but there is little evidence that treating airway reactivity in patients with CF is of clinical importance as a routine measure in the absence of clinical asthma. Definite subjective improvement in symptoms or improved sputum production when a bronchodilator precedes chest physical therapy should be sought to justify continued use in individual patients.

The Effect of Sevoflurane and Desflurane on Upper Airway Reactivity

Although bronchial reactivity can be assessed by changes in airway resistance, there is no well-accepted measure of upper airway reactivity during anesthesia. The authors used the stimulus of endotracheal tube cuff inflation and deflation to assess changes in airway reactivity in patients anesthetized with sevoflurane and desflurane. Sixty-four patients classified as American Society of Anesthesiologists physical status I or II participated in this randomized, double-blind study. Patients were anesthetized with either sevoflurane or desflurane at 1.0 and 1.8 minimum alveolar concentration (MAC). The trachea was stimulated by inflating the endotracheal tube cuff. A blinded observer assessed the severity of patient response to the stimulus and changes in hemodynamic variables. The process was repeated at the second MAC treatment condition. At 1.0 MAC, patients anesthetized with desflurane had a more intense response and a greater likelihood of significant coughing and associated hemodynamic changes (both at P < 0.05). At 1.8 MAC, sevoflurane and desflurane both suppressed clinically significant responses to tracheal stimulation. Interrater reliability was excellent for this measure of upper airway reactivity (P < 0.001). The assessment of the cough response to tracheal stimulation by endotracheal tube cuff inflation is a reliable and clinically meaningful measure of upper airway reactivity. At 1.0 MAC, sevoflurane is superior to desflurane for suppressing moderate and severe responses to this stimulus.