Effects of Inhaled Fluticasone on Upper Airway during Sleep and Wakefulness in Asthma: A Pilot Study.

J Clin Sleep Med. 2014;10(2):183-93

Authors: Teodorescu M, Xie A, Sorkness CA, Robbins J, Reeder S, Gong Y, Fedie JE, Sexton A, Miller B, Huard T, Hind J, Bioty N, Peterson E, Kunselman SJ, Chinchilli VM, Soler X, Ramsdell J, Loredo J, Israel E, Eckert DJ, Malhotra A

Abstract
STUDY OBJECTIVE: Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness.
STUDY DESIGN: 16-week single-arm study.
PARTICIPANTS: 18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted).
INTERVENTIONS: High dose (1,760 mcg/day) inhaled FP.
MEASUREMENTS: (1) UAW collapsibility (passive critical closing pressure [Pcrit]); (2) tongue strength (maximum isometric pressure-Pmax, in KPa) and endurance-time (in seconds) able to maintain 50% Pmax across 3 trials (Ttot)-at anterior and posterior locations; (3) fat fraction and volume around UAW, measured by magnetic resonance imaging in three subjects.
RESULTS: Pcrit overall improved (became more negative) (mean ± SE) (-8.2 ± 1.1 vs. -12.2 ± 2.2 cm H2O, p = 0.04); the response was dependent upon baseline characteristics, with older, male gender, and worse asthma control predicting Pcrit deterioration (less negative). Overall, Pmax increased (anterior p = 0.02; posterior p = 0.002), but Ttot generally subsided (anterior p = 0.0007; posterior p = 0.06), unrelated to Pcrit response. In subjects studied with MRI, fat fraction and volume increased by 20.6% and 15.4%, respectively, without Pcrit changes, while asthma control appeared improved.
CONCLUSIONS: In this study of young, predominantly female, otherwise healthy subjects with well-controlled asthma and stiff upper airways, 16-week high dose FP treatment elicited Pcrit changes which may be dependent upon baseline characteristics, and determined by synchronous and reciprocally counteracting local and lower airway effects. The long-term implications of these changes on sleep disordered breathing severity remain to be determined.
CITATION: Teodorescu M; Xie A; A. Sorkness CA; Robbins J; Reeder S; Gong Y; Fedie JE; Sexton A; Miller B; Huard T; Hind J; Bioty N; Peterson E; Kunselman SJ; Chinchilli VM; Soler X; Ramsdell J; Loredo J; Israel E; Eckert DJ; Malhotra A. Effects of inhaled fluticasone on upper airway during sleep and wakefulness in asthma: a pilot study. J Clin Sleep Med 2014;10(2):183-193.

PMID: 24533002 [PubMed - in process]

Nasal Polyposis: Current Trends.

Indian J Otolaryngol Head Neck Surg. 2014 Jan;66(Suppl 1):16-21

Authors: Rajguru R

Abstract
Nasal polyps (NP) are one of the most common inflammatory mass lesions of the nose, affecting up to 4% of the population. They present with nasal obstruction, anosmia, rhinorrhoea, post nasal drip, and less commonly facial pain. Their etiology remains unclear, but they are known to have associations with allergy, asthma, infection, fungus, cystic fibrosis, and aspirin sensitivity. However, the underlying mechanisms interlinking these pathologic conditions to NP formation remain unclear. Also strong genetic factors are implicated in the pathogenesis of NP, but genetic and molecular alterations required for its development and progression are still unclear. Management of NP involves a combination of medical therapy and surgery. There is good evidence for the use of corticosteroids (systemic and topical) both as primary treatment and as postoperative prophylaxis against recurrence, but the prolonged course of the disease and adverse effects of systemic steroids limits their use. Hence several new drugs are under trial. Surgical treatment has been refined significantly over the past 20 years with the advent of endoscopic sinus surgery and, in general, is reserved for cases refractory to medical treatment. Recurrence of the polyposis is common with severe disease recurring in up to 10% of patients. Over the last two decades, increasing insights in the pathophysiology of nasal polyposis opens perspective for new pharmacological treatment options, with eosinophilic inflammation, IgE, fungi and Staphylococcus aureus as potential targets. A better understanding of the pathophysiology underlying the persistent inflammatory state in NP is necessary to ultimately develop novel pharmacotherapeutic approaches. In this paper we present the newer treatment options available for better control and possibly cure of the disease.

PMID: 24533355 [PubMed - as supplied by publisher]

Related Articles

Immune-Mediated Diseases and Microbial Exposure in Early Life.

Clin Exp Allergy. 2014 Feb 17;

Authors: Bisgaard H, Bønnelykke K, Stokholm J

Abstract
The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system, and certain exposures may have detrimental effects in the earliest life, but no or even beneficial effects later. The human microbiome and infections are candidates as intermediary in the interaction between the host and the environment. The evidence seems inconsistent as infections as well as particular colonization patterns in neonates drives both short-term and long-term asthma symptoms while, on the other hand, the composition of the microbiome in early life may protect against asthma and allergy in later life. This apparent contradiction may be explained by a deeper disease heterogeneity than we are currently able to discriminate, and in particular the indiscriminate lumping together of different diseases into one atopic disease category. Also, the microbiome needs a differentiated understanding, considering balance between microbial groups, diversity, and microbial genetic capability. Furthermore, the effects of the microbial exposure may only affect individuals with certain susceptibility genes. Few of the observations have been replicated and publication bias is likely. Therefore, we are still far from understanding, or having proved, causal effects of the human microbiome. Still, the microbiome-gene interaction is a fascinating paradigm that fosters exiting research and promises a breakthrough in the understanding of the mechanisms driving asthma, allergy and eczema, and potentially also other immune-mediated non-communicable diseases. This article is protected by copyright. All rights reserved.

PMID: 24533884 [PubMed - as supplied by publisher]

Related Articles

Allergic rhinitis: current options and future perspectives.

Curr Opin Allergy Clin Immunol. 2014 Feb 14;

Authors: Braido F, Arcadipane F, Marugo F, Hayashi M, Pawankar R

Abstract
PURPOSE OF REVIEW: Allergic rhinitis due its high prevalence and burden needs to be properly treated. The disease's clinical features impose well tolerated drugs usable for long-term treatment. Nowadays, second-generation antihistamines and inhaled steroids represent the milestone of rhinitis therapy. The aim of the present review is to provide an update on allergic rhinitis treatment. A particular attention has been deserved to clinical trials, published in the last year that assess the efficacy and safety of new formulation of available drugs or new molecules.
RECENT FINDINGS: Available and new drugs under investigation seem able to control rhinitis symptoms without a significant patient's burden. The challenge for the next years will be to improve treatment adherence rather than to introduce new drugs.
SUMMARY: Allergic Rhinitis and its Impact on Asthma guidelines have brought attention to allergic rhinitis and its impact on asthma, but have also proposed a new classification in terms of symptoms severity and persistence useful for tailoring treatment on patients' phenotypes. Their further dissemination is needed; furthermore, they represent a cornerstone for the scientific community through a continuous update on relevant issues such as rhinitis phenotypes, disease management on the basis of new treatments, clinical trials transferability in real life, and allergic rhinitis management in public health programs.

PMID: 24535140 [PubMed - as supplied by publisher]