Voice bubbling therapy for vocal cord dysfunction in difficult-to-treat asthma - a pilot study.

OBJECTIVE: Dysfunctional breathing often coexists with asthma and complicates asthma control, especially in difficult-to-treat asthma. Voice bubbling therapy (VBT) by a specialized speech therapist may influence the breathing pattern. This pilot study investigated the effect of voice bubbling therapy (VBT) in participants with difficult-to-treat asthma, who fulfilled criteria for dysfunctional breathing pattern. METHOD: Twenty-four patients were randomized between VBT and usual care (UC). VBT is blowing into a glass (resonance) tube (28 cm in length, 0.9 cm inner diameter) which ends in a bowl of water (1.5 litre). Lung function, capillary blood gas and questionnaires were measured at baseline, at 6 and 18 weeks of follow up. RESULTS: No difference in ACQ and quality of life was found after VBT compared to UC group. However, after six weeks of bubbling therapy, pCO2 levels measured in capillary blood gas were higher (baseline median (IQR) pCO2 = 33.00 (17.25 - 38.6) mmHg; week 6 pCO2 = 36.00 (29.00 - 42.3) mmHg) p = 0.01. Moreover, ΔpCO2 (baseline - 18 weeks of follow up) was significantly correlated with ΔAQLQ (rs = 0.78, p = 0.02). CONCLUSION: VBT in participants with difficult-to-treat asthma resulted in a higher average pCO2 level, indicating the treatment may improve hyperventilation. However, this did not improve asthma control or quality of life. VBT may have value for a better management of asthma related symptoms.

Validated safety predictions of airway responses to house dust mite in asthma.

BACKGROUND: House dust mite (HDM) is the most common aeroallergen causing sensitization in many Western countries and is often used in allergen inhalation challenges. The concentration of inhaled allergen causing an early asthmatic reaction [provocative concentration of inhaled allergen causing a 20% fall of forced expiratory volume in 1 s (FEV(1))(PC(20) allergen)] needs to be predicted for safety reasons to estimate accurately the severity of allergen-induced airway responsiveness. This can be accomplished by using the degree of non-specific airway responsiveness and skin sensitivity to allergen. OBJECTIVE: We derived prediction equations for HDM challenges using PC(20) histamine or PC(20) methacholine and skin sensitivity data obtained from patients with mild to moderate persistent asthma and validated these equations in an independent asthma population. METHODS: PC(20) histamine or PC(20) methacholine, skin sensitivity, and PC(20) allergen were collected retrospectively from 159 asthmatic patients participating in allergen challenge trials. Both the histamine and methacholine groups (n=75 and n=84, respectively), were divided randomly into a reference group to derive new equations to predict PC(20) allergen, and a validation group to test the new equations. RESULTS: Multiple linear regression analysis revealed that PC(20) allergen could be predicted either from PC(20) methacholine only ((10)log PC(20) allergen=-0.902+0.741.(10)log PC(20) methacholine) or from PC(20) histamine and skin sensitivity (SS) ((10)log PC(20) allergen=-0.494+0.231.(10)log SS+0.546.(10)log PC(20) histamine). In the validation study, these new equations accurately predicted PC(20) allergen following inhalation of HDM allergen allowing a safe starting concentration of allergen of three doubling concentrations below predicted PC(20) allergen in all cases. CONCLUSION: The early asthmatic response to inhaled HDM extract is predominantly determined by non-specific airway responsiveness to methacholine or histamine, whereas the influence of the cutaneous sensitivity to HDM appears to be rather limited. Our new equations accurately predict PC(20) allergen and hence are suitable for implementation in HDM inhalation studies.

Bronchial matrix and inflammation respond to inhaled steroids despite ongoing allergen exposure in asthma.

BACKGROUND: Inflammatory and structural changes of the airway mucosa are chronic features of asthma. The mechanisms underlying these changes and their modulation by steroid prophylaxis have not been clarified. OBJECTIVE: We postulated that asymptomatic ongoing allergen exposure could drive airway inflammation as well as changes in the extracellular matrix (ECM), and that inhaled steroids could prevent this. METHODS: Therefore, we exposed patients with mild asthma to 2 weeks of repeated low-dose allergen, with concomitant inhaled steroid or placebo treatment. Bronchial biopsies, which were taken before and after this exposure, were stained and digitally analysed. The ECM proteins in asthmatics were also compared with a normal control group. RESULTS: Low-dose allergen exposure alone resulted in a significant increase of bronchial epithelial macrophages. Despite ongoing allergen exposure, inhaled steroids reduced the numbers of mucosal eosinophils, neutrophils and T lymphocytes. At baseline, the mean density of the proteoglycans (PGS) biglycan and decorin were, respectively, higher and lower in the bronchial mucosa of asthmatics as compared with normal controls. Steroid treatment, during allergen exposure, increased the mean density of the PGS biglycan and versican. CONCLUSION: We conclude that chronic allergen exposure induces inflammatory changes in the bronchial mucosa. Despite ongoing allergen exposure, steroid treatment decreases mucosal inflammatory cells while altering PG density. The latter observation highlights the need to examine steroid-induced changes closely in the airway structure in patients with asthma.

Interleukin-1beta and interleukin-1ra levels in nasal lavages during experimental rhinovirus infection in asthmatic and non-asthmatic subjects.

BACKGROUND: Exacerbations of asthma are often associated with rhinovirus (RV)-induced common colds. During experimental RV-infection in healthy subjects, increased levels of the pro-inflammatory mediator IL-1beta and the anti-inflammatory IL-1 receptor antagonist (IL-1ra) have been found in nasal lavage. OBJECTIVE: We postulated that the balance between nasal pro- and anti-inflammatory mediator expression is disturbed in asthma, resulting in more extensive inflammation following RV-exposure in asthma. METHODS: We determined IL-1ra, IL-1beta, and IL-8 in nasal lavages (days -2, 3, and 6) of non-asthmatics and asthmatics (with and without pre-treatment with the inhaled steroid budesonide) before and after experimental RV16-infection (days 0 and 1). RESULTS: Following RV16-infection, a significant increase in IL-8 was observed in the placebo- and budesonide-treated asthmatics (P=0.033 and 0.037, respectively), whereas IL-1beta only increased in the two asthma groups combined (P=0.035). A small, but significant, increase in IL-1ra was only observed in the budesonide-treated asthmatics (P=0.047). At baseline, IL-1ra levels were significantly higher in the non-asthmatics than in the placebo-treated asthmatics (P=0.017). CONCLUSION: These results demonstrate differences between non-asthmatic and asthmatic subjects in the basal levels of nasal cytokines and their inhibitors, and in the effect of experimental RV-infection on these levels. The results indicate that RV may enhance inflammation more markedly in asthmatics, and suggest that this may in part be explained by lower IL-1ra levels. In addition, the observation that budesonide-treatment may result in higher nasal IL-1ra levels supports the hypothesis that steroids act in part by increasing the endogenous anti-inflammatory screen.

Rhinovirus infection in nonasthmatic subjects: effects on intrapulmonary airways.

The common cold is a highly prevalent, uncomplicated upper airway disease. However, rhinovirus (RV) infection can lead to exacerbation of asthma, with worsening in airway hyperresponsiveness and bronchial inflammation. The current authors questioned whether such involvement of the intrapulmonary airways is disease specific. Twelve nonatopic, healthy subjects (forced expiratory volume in one second (FEV1) >80% predicted, provocation concentration causing a 20% fall in FEV1 (PC20) >8 mg x mL(-1)) were experimentally infected with RV16. Next to PC20 and the maximal response to methacholine (MFEV1 and MV'40p), the numbers of mucosal inflammatory cells and epithelial intercellular adhesion molecule (ICAM)-1 expression in bronchial biopsies were assessed before and 6 days after RV16 inoculation. RV16 infection induced a small but consistent increase in maximal airway narrowing, without a change in PC20. There was a significant increase in bronchial epithelial ICAM-1 expression after RV16, whereas inflammatory cell counts did not change. Nevertheless, the change in the number of submucosal CD3+ cells was correlated with the change in MV'40p. In conclusion, rhinovirus infection in normal subjects induces a limited, but significant increase in maximal airway narrowing, which is associated with changes in bronchial T-cell numbers. Together with the upregulation of bronchial epithelial intercellular adhesion molecule-1, these findings indicate that, even in healthy subjects, rhinovirus infection affects the intrapulmonary airways.