The role of impulse oscillometry in the management of asthma when forced expiratory maneuvers are contraindicated: case series and literature review.

Objectives: The impulse oscillometry system (IOS) provides an alternative method of lung function testing for patients in whom forced expiratory manoeuvres are contraindicated, such as those with inherited vascular connective tissue disorders. Here we examine the role of IOS in the diagnosis and monitoring of asthma in such patients through a clinical case series and literature review.Methods: The clinical case series comprised of data from 12 patients with inherited connective tissue disorders representing 32 clinical encounters. Of these, 11 encounters were for asthma diagnosis and 21 were for asthma monitoring. Symptoms, exhaled nitric oxide (FeNO) and IOS were assessed at each encounter.Results: In the clinical case series, 5 of 6 patients with likely asthma (as determined by physician review and exhaled nitric oxide testing) had abnormal IOS parameters compared with 0 of 5 of those with unlikely asthma. In the monitoring group, 11 encounters resulted in treatment escalation (demonstrating suboptimal control), and 8 resulted in no change to treatment (good control). Six of 11 of those with suboptimal control had abnormalities in ≥3 IOS parameters, with R5 and R5-20 most frequently affected. Only 1 of 8 of those with good control had abnormalities in ≥3 IOS parameters.Conclusions: IOS can be used as an alternative to conventional lung function testing to support the diagnosis and monitoring of asthma when forced expiratory manoeuvres are contraindicated. Larger studies are required to establish severity and treatment escalation thresholds and provide clearer comparisons with spirometry values.

TGF-ß2 decreases baseline and IL-13-stimulated mucin production by primary human bronchial epithelial cells.

INTRODUCTION: Mucus hypersecretion is a major contributor to asthma pathology and occurs as part of a spectrum of structural changes termed airway wall remodeling. Transforming growth factor (TGF)-ß is proposed to play a key role in regulating airway matrix remodeling although less is known about the specific action of TGF-ß isoforms in regulating mucus production. METHODS: Primary human bronchial epithelial (HBE) cells cultured at air-liquid interface were treated with exogenous TGF-ß(1), TGF-ß(2), and/or a Th2 cytokine, interleukin (IL)-13. Expression and production of respiratory mucins, MUC5AC and MUC5B, were analyzed by real-time PCR, agarose gel electrophoresis, and western blotting. A murine-transformed Clara cell line (mtCC1-2) transfected with a luciferase reporter driven by the Muc5ac promoter containing Smad4 site-mutated cis sequences was used to determine whether exogenous TGF-ß(2) affects Muc5ac promoter function. RESULTS: Surprisingly, TGF-ß(1) showed no measurable effect on MUC5AC or MUC5B production by HBE cells whereas TGF-ß(2) caused a decrease in both MUC5AC and MUC5B mRNA and protein. Dual treatment with TGF-ß(2) and IL-13 partially attenuated the increase in mucin production found with IL-13 alone. This effect was confirmed by using mtCC1-2 cells where addition of TGF-ß(2) reduced the ability of IL-13/EGF to induce Muc5ac promoter expression in wild-type cells; however, this decrease was absent in mutant promoter-transfected cells. DISCUSSION AND CONCLUSION: Findings suggest that normal regulation of MUC5AC and MUC5B production by HBE cells is TGF-ß isoform-specific and that TGF-ß(2) downregulates both MUC5AC and MUC5B. Furthermore, TGF-ß(2) controls baseline and IL-13-driven Muc5ac promoter function in murine Clara cells via an endogenous Smad4 recognition motif.

The utility of antifungal agents for asthma.

PURPOSE OF REVIEW: Recent work demonstrates that patients with refractory asthma are likely to be sensitized to environmental fungi and that specific antifungal treatments may be of benefit to this group. RECENT FINDINGS: The relationships among fungal sensitization, exposure and asthma severity are imperfectly understood. Exposure to environmental fungi occurs ubiquitously and there is emerging evidence that internal airways colonization could be a source of ongoing exposure. Antifungal treatments appear to improve asthma-related quality of life. Such treatments are generally well tolerated but there are potential side-effects. The mechanisms behind the clinical improvements are not yet fully established. SUMMARY: Antifungal treatments are used in some centres for patients with refractory asthma. Further research needs to explore the questions of patient selection, optimum duration of therapy and the prediction and management of azole-corticosteroid drug interactions. Advances in our understanding of the fungal molecular allergome and in our understanding of the allergic importance of small hyphal fragments may help to more precisely define the relationships among fungal sensitization, exposure and asthma severity.

Intranasal air sampling in homes: relationships among reservoir allergen concentrations and asthma severity.

BACKGROUND: The relationship among inhaled allergen exposure, sensitization, and asthma severity is unknown. OBJECTIVES: To investigate the relationship among personal allergen exposure, reservoir dust allergen concentrations, and physiological measures of asthma severity; to examine the numbers of particles inspired that react with autologous IgE and IgG4. METHODS: A total of 117 patients with asthma wore 5 nasal air samplers (NASs) at home: 1 each for exposure to mite, cat and dog allergens, NAS-IgE, and NAS-IgG4. NASs were processed by HALOgen assay for allergen measurement and incubated with autologous serum for detection of NAS-IgE and NAS-IgG4. Reservoir allergen concentrations were measured by ELISA. Subjects' asthma severity was ascertained by measurement of lung function, exhaled nitric oxide, and nonspecific bronchial reactivity to histamine. RESULTS: Nasal air sampler counts correlated with reservoir concentrations for cat (r=0.31; P=.001) and dog (r=0.20; P=.03) but not mite allergen (r=0.001; P=1.0). There was no significant relationship between sensitization with exposure measured by NAS to any allergen and PD20FEV1 (F[3,60]=1.60; P=.20); however, sensitization with exposure in dust reservoirs had significant effects on PD20FEV1 for any allergen (F[3,59]=3.12; P=.03), cat (F[3,59]=3.77; P=.01), and mite (F[3,59]=2.78; P=.05), but not dog (F[3,59]=1.06; P=.37). We repeated the analysis with separate variables for sensitization and exposure, controlling for the confounders; sensitization but not exposure conferred lower PD20FEV1 values. However, increasing cat allergen exposure was associated with improving bronchial reactivity in not cat-sensitized patients. NAS-IgE and NAS-IgG4 counts bore no relationship to any measure of asthma severity. CONCLUSION: Nasal air samplers confer no advantage over reservoir dust analysis for studies of asthma severity. CLINICAL IMPLICATIONS: In common with other measures of exposure, single nasal air samples do not provide a useful measure of home allergen exposure for the individual patient with allergic asthma.

Controlling indoor allergens.

OBJECTIVES: Reading of this article reinforces the reader's knowledge of the role of allergen exposure in relation to asthma and its severity, as well as the relevance of allergen avoidance in the treatment of asthma. DATA SOURCES: Initial literature search for existing evidence-based guidelines, reviews, and meta-analyses was carried out, and further literature searches were performed to review individual randomized controlled trials. Evidence level was graded according to the Scottish Intercollegiate Guidelines Network recommendations. RESULTS: There is good evidence for the link between mite and cockroach allergen exposure and sensitization, and between sensitization and asthma. For pet allergens, some studies found that exposure to pets in early life was associated with specific immunoglobulin E sensitization and allergic disease later in childhood, whereas others reported a protective effect. The effectiveness of allergen reduction in the treatment of asthma is suggested by studies in which the patients improve substantially when moved into the low-allergen environment of hospitals or high-altitude sanatoria. Because of limitations in the design of the most clinical of studies, we do not yet have a conclusive answer on the effectiveness of domestic aeroallergen avoidance. CONCLUSIONS: Minimizing the impact of identified environmental risk factors is an important first step to reduce the severity of asthma. Although environmental control is difficult, it should be an integral part of the overall management of sensitized patients. However, what is unclear is which patients would benefit and by how much, and whether the intervention is cost-effective. These questions will be answered satisfactorily only by large randomized trials.

High-efficiency particulate arrest-filter vacuum cleaners increase personal cat allergen exposure in homes with cats.

BACKGROUND: On the basis of experimental chamber studies, vacuum cleaners with double-thickness bags and integral high-efficiency particulate arrest (HEPA) air filters are claimed to reduce airborne allergen levels and are currently recommended to allergic patients. OBJECTIVES: The objective of this study was to investigate the effect of vacuum cleaning on personal inhaled cat allergen exposure in homes with cats. METHODS: Five unused new vacuum cleaners were compared with an old non-HEPA filter vacuum cleaner. Each vacuum cleaner was tested in an experimental chamber and in 5 homes with cats. Inhaled cat allergen was measured by nasal air sampling. RESULTS: New vacuum cleaners failed to leak any allergen in the experimental chamber. There was a significant increase in inhaled cat allergen during vacuum cleaning in homes (F = 48.39, df = 1.4, P =.002) with no difference between the old vacuum cleaner and the unused new vacuum cleaners (5-fold and 3-fold increase compared to baseline, respectively; F = 0.005, df = 1.4, P =.95). CONCLUSIONS: The use of new HEPA-filter vacuum cleaners increases inhaled cat allergen in homes with cats. The use of HEPA-filter modern vacuum cleaners to reduce pet allergen exposure in the homes of pet owners should not be justified merely on the basis of experimental chamber data.