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This study aims to identify associations between nocturnal asthma awakenings and functional health outcomes in a cohort of teenagers with asthma.We analyzed baseline data from teenagers enrolled in SB-ACT, an NIH-funded RCT. During an at-home baseline survey, teenagers with asthma answered questions about demographics, recent asthma symptoms, and functional health outcomes. We conducted regression analyses to explore the relationship between persistent nocturnal asthma symptoms (≥2 nights of nocturnal asthma awakenings in the past 14 days) and functional health measures.Of the 430 teens enrolled (Participation rate = 79%, Mean Age = 13.4), 30% reported persistent nocturnal asthma symptoms. Compared to teens with intermittent nocturnal asthma symptoms, teens with persistent nocturnal asthma symptoms were more likely to report physical limitation during strenuous activities (OR = 1.9, 1.3-3.0), moderate activities (OR = 1.9, 1.2-3.1), and school gym (OR = 2.4, 1.5-3.8). They were also more likely to report depressive symptoms (OR = 2.3, 1.5-3.6), more asthma-related school absenteeism in the past 14 days (0.81 vs 0.12, plt; 0.01) and poorer quality of life (4.6 vs 5.9, plt; 0.01). These findings remained significant when controlling for daytime asthma symptoms, weight status, race, ethnicity, gender, age, and smoke exposure.In this cross-sectional study, persistent nighttime asthma symptoms were associated with poor functional health outcomes among teens, independent of day-time symptoms. Identifying nighttime symptoms and improving asthma control at night may positively impact daily functioning for these teens.

Mustafa Abdo,1 Frederik Trinkmann,2,3 Anne-Marie Kirsten,4 Heike Biller,1 Frauke Pedersen,1,4 Benjamin Waschki,1 Erika Von Mutius,5 Matthias Kopp,6,7 Gesine Hansen,8 Klaus F Rabe,1 Thomas Bahmer,1,9,&ast; Henrik Watz4,&ast; On behalf of the ALLIANCE study group1LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; 2Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany; 3Department of Biomedical Informatics, Heinrich-Lanz-Center, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany; 4Pulmonary Research Institute at the LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; 5Dr von Hauner Children’s Hospital, Ludwig Maximilians University of Munich, Comprehensive Pneumology Center Munich, German Center for Lung Research (DZL), and Institute of Asthma and Allergy Prevention, Helmholtz Centre, Both Munich, Germany; 6Department of Pediatric Respiratory Medicine, Inselspital, University Children’s Hospital of Bern, University of Bern, Bern, Switzerland; 7Division of Pediatric Pneumology & Allergology, University Hospital Schleswig-Holstein-Campus Luebeck, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Luebeck, Germany; 8Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany; 9University Hospital Schleswig-Holstein-Campus Kiel, department for Internal Medicine I, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Kiel, Germany&ast;These authors contributed equally to this workCorrespondence: Mustafa AbdoLungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Wöhrendamm 80, Grosshansdorf, 22927, GermanyTel +49 4102 601 2412Email m.abdo@lungenclinic.deRationale: Small airway dysfunction (SAD) is a frequent feature of asthma that has been linked to disease severity and poor symptom control. However, little is known about the role of SAD in nocturnal asthma.Objective: To study the association between the severity of SAD and frequency of nocturnal symptoms compared to conventional lung function testing.Methods: We assessed the frequency of self-reported nocturnal symptoms through the asthma control test. We studied the impact of nocturnal asthma using the Asthma Quality of Life Questionnaire (AQLQ) and the Multidimensional Fatigue Inventory (MFI-20). We assessed the lung function using spirometry, body plethysmography, impulse oscillometry, single and multiple inert gas washout and measured markers of T2-inflammation (blood and sputum eosinophils; fractional exhaled nitric oxide (FeNo)). We stratified the patients according to the presence and frequency of nocturnal asthma.Results: A total of 166 asthma patients were enrolled in the analysis. Eighty-seven patients (52%) reported to have nocturnal symptoms at least once in the last four weeks. The odds ratio of nocturnal asthma correlated with the severity of all non-spirometric measures of SAD, yet neither with airflow obstruction (FEV1 and FEV/FVC) nor with large airway resistance (R20). Patients with frequent nocturnal asthma (n = 29) had a numerical increase of T2 markers and more severe SAD, as indicated by all non-spirometric measures of SAD (all p-values < 0.05), worse overall asthma control, increased fatigue and reduced quality of life (all p-values < 0.01) compared to patients with infrequent nocturnal asthma (n = 58) or patients without nocturnal asthma (n = 79). We identified 63 patients without airflow obstruction, nearly 43% of them (n = 27) had nocturnal asthma. In this subgroup, only markers of air trapping and ventilation heterogeneity were significantly elevated and correlated with the frequency of nocturnal symptoms: LCI (Spearman’s coefficient = − 0.42, p < 0.001), RV% (− 0.32, p = 0.02).Conclusion: SAD is closely associated to asthma with nocturnal symptoms. Spirometry might underestimate the broad spectrum of distal lung function impairments in this population of patients.Keywords: small airway dysfunction, nocturnal asthma, ventilation heterogeneity, air trapping

Zusammenfassung Einleitung Wesentlicher Bestandteil der Asthmakontrolle ist die Symptomfreiheit tagsüber und nachts. Die akustische Langzeitregistrierung ermöglicht eine objektive Erfassung respiratorischer Symptome. In dieser prospektiven Beobachtungsstudie mit Pilotcharakter wurde untersucht, wie häufig nächtlich auftretende respiratorische Symptome wie Husten und Giemen bei stabil eingestellten Asthmatikern zu finden sind. Methode Nächtlich auftretender Husten und Wheezing wurden mithilfe des LEOSound-Monitorsystems bei 40 Patienten mit stabilem Status aufgezeichnet. Die Patienten waren zum Zeitpunkt der ärztlichen Vorstellung respiratorisch beschwerdefrei, der Asthmakontrolltest (ACT) ergab einen mittleren Score von 23 Punkten. Der FEV1-Wert betrug 84 ± 15 %; der MEF 50 71 ± 27 % und der Rtot 0,48 ± 0,18. Das Alter der Patienten lag bei 35 ± 11 Jahren. Alle Patienten hatten eine antiobstruktive und/oder antiinflammatorische Therapie. Die Fragestellungen waren wie folgt: 1. Wie häufig werden nächtlicher Husten und Giemen bei Patienten mit stabilem Asthma bronchiale gefunden? 2. Unterscheiden sich Patienten mit/ohne nächtlichem/n Husten/Giemen hinsichtlich ACT und Lungenfunktion? Ergebnisse Bei zwei Patienten konnte nächtliches Wheezing mit einer Gesamtdauer von 19 bzw. 55 Minuten nachgewiesen werden. Patient 1 hatte einen persistierenden Nikotinkonsum bei leichtgradiger Atemwegsobstruktion, Patient 2 war Nichtraucher und wies eine deutliche Bronchialobstruktion (FEV1 49 %; MEF 50 27 % und Rtot 0,52 kPas/l) auf. 26 Patienten hatten keinen Husten bzw. ausschließlich solitäre Hustenereignisse. 14 Patienten wiesen nächtliche Hustensalven mit einer Häufigkeit von 4 ± 3 (2 – 13) auf. Bezüglich der Subgruppenanalyse Husten/Nichthusten ergaben sich sowohl hinsichtlich der ACT-Scores als auch der Lungenfunktionsparameter keine relevanten Unterschiede. Die beiden Patienten mit nächtlichem Wheezing wiesen im ACT vergleichsweise niedrige Punktewerte mit 20 und 21 Punkten auf. Diskussion Nächtliches Wheezing und Hustensalven waren bei 2 bzw. 14 der stabil eingestuften Asthmapatienten nachweisbar. Mithilfe der Langzeitregistrierung der Atem- und Atemnebengeräusche ist eine objektive Erfassung von nächtlichem Husten und Wheezing möglich.

BACKGROUND AND OBJECTIVE Unrecognized obstructive sleep apnoea syndrome (OSAS) may lead to poor asthma control despite optimal therapy. We assessed asthma control, airway responsiveness, daytime sleepiness and health status at baseline and 3 months after continuous positive airway pressure (CPAP) treatment among asthma patients with nocturnal symptoms and OSAS. METHODS Patients with nocturnal asthma symptoms despite receiving at least moderate-dose inhaled corticosteroid and long-acting bronchodilators underwent a home sleep study using 'Embletta' portable diagnostic system. Patients with significant OSAS (apnoea-hypopnoea index (AHI) ≥10/h) were randomized to receive either CPAP or conservative treatment for 3 months. RESULTS Among 145 patients recruited, 122 underwent sleep study with 41 (33.6%) having AHI ≥10/h. Patients with significant OSAS had higher BMI (27.4 (5.1) vs 25.1 (4.5) kg/m2 , P = 0.016), bigger neck circumference (36.6 (3.1) vs 34.8 (3.6) cm, P = 0.006) and lower minimum SaO2 (80.7 (6.6) vs 87.2 (3.9) %, P

Objective: The aims and objective of this study to observe the improvement in Nocturnal Asthma symptoms and Quality of Life (QoL) with administration of once daily sustained release theophylline preparation. Background: Nocturnal symptoms are a common part of the asthma. Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV1) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma, which may include improvement in QoL. Methodology: The patient with Chronic Persistent Asthma, both sex, age >18 to 50 years of age and preferably patients with nocturnal exacerbations were included in the study. All patients were diagnosed on the basis of clinical history, physical examination, chest X-ray and pulmonary function tests, in accordance with the clinical criteria for the diagnosis by the GINA. The recruitment period was between March 2017 and August 2017 Shaheed Suhrawardy Medical College Hospital, Dhaka. Results: It was observed that 65(92.85%) was found exacerbation free night and 5(7.15%) patients were found exacerbation with sustained release Theophylline. There are significantly improved qualities of life between 1 st follow up to 2 nd follow up, 3 rd follow up and 4 th follow up p

Out of most morbid disorders, the disease shwas is also becoming a major health problem of the society. Difficulties in breathing, cough are common health complains which everyone experiences throughout their life with different magnitude. Such complains are found in every age group. Dyspnea due to respiratory diseases comes under ShwasaRoga. Maha- Urdhva-Chinna-Tamaka and Kshudra are the types of ShwasaRoga. Bronchial asthma is a chronic inflammatory disease of airways characterized by cough, difficulty in breathing and wheeze. Exposure to dust, smoke, recurrent respiratory infections and climatic changes are chief triggering factors of this disease. Bronchial asthma and its associated features clinically correspond to the Tamaka Shwasa described in Ayurveda.

Both asthma and obstructive sleep apnoea cause sleep disturbance, daytime sleepiness and diminished quality of life. Continuous positive airway pressure (CPAP) is efficient in reducing symptoms related to sleep apnoea. Here we report the impact of long-term use of CPAP on asthma symptoms. A survey questionnaire was distributed to all of our obstructive sleep apnoea patients with CPAP therapy in 2013. We used the Finnish version of the Asthma Control Test (TM) (ACT) and a visual analogue scale (0 = no symptoms, 100 = severe asthma symptoms). Asthma was defined as self-reported physician-diagnosed disease and a special reimbursement for asthma medication by the Social Insurance Institution. We sent 2577 questionnaires and received 1586 answers (61 %). One hundred ninety-seven patients were asthmatics with a prevalence of asthma among CPAP users of 13 %. We studied 152 patients (58 females) whose CPAP therapy was initiated after starting asthma medication. Their mean (SD) age was 62 (10) years, duration of CPAP 5.7 (4.7) years and their CPAP daily use was 6.3 (2.4) h. Self-reported asthma severity decreased significantly from 48.3 (29.6) to 33.1 (27.4) (p

Objective: Youth with asthma are at-risk for sleep difficulties due to nocturnal asthma symptoms. Sleep hygiene, or the ability to practice consistent sleep behaviors and habits, impacts yo...

Asthma is a chronic inflammatory lung disease characterized by reversible obstruction of airways and bronchial hyperresponsiveness. In recent years there has been a growing interest in the role of the small airways in asthma and there is increasing evidence that they contribute significantly to the clinical expression of asthma. Numerous studies have shown that inflammation is present in the small airways of patients with asthma and that it may be more intense than that found in the large airways, particularly in severe asthma, nocturnal asthma, coexisting asthma and obesity and asthma in smokers. Currently there is no accepted single lung function parameter to detect small airways dysfunction. Recent data show that impulse oscillometry is a promising diagnostic tool to assess the involvement of the small airways. The use of corticosteroids in extrafine formulation, whether alone or in fixed combinations with long-acting b2 agonists, improves drug distribution throughout the bronchial tree, enhancing the therapeutic effect with lower doses of drugs.

Background: Asthma is a common ailment with a larger circadian difference. Nocturnal Asthma (NA) is an inconstant exacerbation of asthmatic condition related to the rise in warning sign during the night time and there is a need for its treatment addressing air route alertness and decline in lung functions. These symptoms are linked to sleep or known as circadian events. Chronotherapeutics is a management system based on an in-vivo drug accessibility programmed to check the rhythms of ailment in a direction to improve the therapeutic outcomes by suppressing the side effects. This review aims to provide an overview of NA, chronotherapeutics for the treatment of NA, bilayer tablets, and advanced techniques involved in the fabrication of bilayer tablets. The review also discusses some of the related patents. Methods: Relevant literature about the latest developments and updated information related to NA, chronotherapeutics and bilayer tablets has been very widely searched on different biomedical literature programs such as Google, Web of Science, PubMed portals, etc. Bilayer tablet mediated chronotherapy has gained significant attention and consideration as it is developed and fabricated based on the body’s circadian rhythm. Bilayer tablets can deliver the bioactive compounds at an appropriate time, place as well as amount and site. Results: Available literature advocated that the bilayer matrix tablet containing a single drug in the sustained release film and fast releasing film, may be beneficial for the chronic diseases like asthma, migraine, diabetes, hypertension and inflammation which usually require immediate as well as maintained therapeutic effect. Conclusion: The application of nanotechnology in the arena of medicine will transform the diagnosis and treatment strategies of a wide range of diseases in the upcoming years. The findings of this review confirm the importance of bilayer tablet based chronotherapy in nocturnal asthma.

Relevant indications for tiotropium Respimat in adult patients with bronchial asthma (BA) were reviewed. This consensus represents a collaborative effort of members of the Executive Group of Russian Respiratory Society. The Group consisted of clinicians, pharmacologists and researchers with recognized expertise in therapeutic field. The draft of the recommendations was prepared by initiative group. Each point of the recommendation was discussed during Executive group meeting and was accepted by vote of majority members. Final version of the consensus statement was approved by each member of Executive group. As concluded, tiotropium Respimat could be recommended for adult patients with bronchial asthma as: 1) add-on therapy in patients with severe and moderate severe non-controlled BA on GINA step 3–5 (ICS and LABA, including oral steroids or other controllers, or high doses ICS monotherapy); 2) add-on therapy in patients with asthma-COPD overlap syndrome (ACOS); 3) add-on therapy to ICS in case of side effects, contraindications for use or individual intolerance of LABA; 4) additional indications to consider use of tiotropium Respimat may include: smoking, positive SABA reversibility test, predominant nocturnal asthma symptoms.

Background: Mental health conditions are becoming more common and may have implications on childhood asthma. Objectives: We examined the association between childhood asthma and mental health conditions and if asthma outcomes were worse among children with both asthma and a mental health condition. Methods: In 2013 we completed a cross-sectional survey of urban and rural dwelling children (5-14 years, n=3,509) from Saskatchewan, Canada. Surveys were distributed through randomly selected schools for parental self-completion. Asthma was based on report of a previous doctor9s diagnosis. Presence of a mental health condition was based on a report of doctor’s diagnosis of emotional, psychological, nervous difficulties, or ADD/ADHD. Allergy was based on a report of a respiratory allergy, hayfever, or eczema. Results: Asthma prevalence was 19.1% while the prevalence of mental health conditions was 5.5%. Among those without asthma, 4.8% had a mental health condition while among those with asthma, the prevalence was 8.2% (p Conclusions: Children with asthma are more likely to experience a mental health condition than children without asthma and this may be related to worse outcomes (nocturnal asthma symptoms). The relationship appears to be driven by allergic disease.

Background: We have previously shown that when asthmatics go supine, fluid shifts out of the legs, accumulates in the thorax, and exacerbates lower airway narrowing. In the retrospective analysis of our previous work presented here, we test the hypothesis that the sensitivity of this process relates inversely to baseline caliber of the lower airways. Methods: Eighteen healthy (six women) and sixteen asthmatic subjects (nine women) sat for 30 min, and then lay supine for 30 min. While supine, lower body positive pressure (LBPP, 40 mm Hg) was applied to displace fluid from the legs similar in amount to the overnight fluid shift. Respiratory resistance and reactance at 5 Hz (R5 and X5) and leg and thoracic fluid volumes (LFV and TFV) were measured at the beginning and end of the supine period. Results: With LBPP, healthy, and asthmatic subjects had similar changes in the LFV and TFV (p = 0.3 and 0.1, respectively). Sensitivity to fluid shift, defined by ΔR5/ΔTFV, was larger in the asthmatics than in the healthy subjects (p = 0.0001), and correlated with baseline R5 in the supine position in the asthmatics (p = 0.7, p = 0.003). No such association was observed in the healthy subjects (p = 0.6). In the asthmatics, women showed a greater reduction in X5 than men with LBPP (p = 0.009). Conclusions: Smaller baseline airway caliber, as assessed by larger R5, was associated with increased sensitivity to fluid shift in the supine position. We conclude that asthmatics with narrower small airways such as obese asthma patients, women with asthma and those with severe asthma may be more sensitive to the effects fluid shift while supine as during sleep.

Small airways disease plays an important role in the pathogenesis of asthma, but assessment of small airways impairment is not easy in everyday clinical practice. The small airways can be examined by several invasive and noninvasive methods, most of which can at present be used only in the experimental setting. Inhalers providing extrafine inhaled corticos - teroid particle sizes may achieve sufficient deposition in the peripheral airways. Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation, ie, on dysfunction in both the central and distal airways in asthmatics, and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes, including nocturnal asthma, severe steroid-dependent or difficult-to-treat asthma, asthma complicated by smoking, elderly asthmatic patients and/or patients with fixed airflow obstruction, and asthmatic children. The relevant randomized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints, but there are certain clinically important endpoints for which the extrafine formulations show additional benefits.

We examined the association between: 1) cortisol levels and asthma or asthma development; 2) cortisol levels upon stress and asthma. In addition, we performed a post hoc meta-analysis on results from the literature.Cortisol, cortisol upon stress, asthma (doctor diagnosis of asthma and/or symptoms and/or treatment in the past 12 months) and asthma development (asthma at a specific survey while not having asthma at the previous survey(s)) were assessed in the TRAILS study (n=2230, mean age at survey 1 11 years, survey 2 14 years and survey 3 16 years). Logistic regression models were used to study associations between: 1) cortisol (cortisol awakening response, area under the curve (AUC) with respect to the ground (AUCg) or with respect to the increase (AUCi), and evening cortisol) and asthma or asthma development; 2) cortisol upon stress (AUCg or AUCi) and asthma. The meta-analyses included nine case-control articles on basal cortisol in asthma.No significant association was found between: 1) cortisol and asthma (age 11 years) or asthma development (age 14 or 16 years); 2) cortisol upon stress and asthma (age 16 years). The metaanalysis found lower morning and evening cortisol levels in asthmatics compared to nonasthmatics; however, the summary estimates were not significant.We found no evidence supporting a role for cortisol in asthma and asthma development.

The purpose of the present study was the development and in vitro/in vivo evaluation of the guar gum based colon -specific compression-coated tablet formulation of theophylline, which can be used for the treatment of nocturnal asthma. The core tablets containing 100 mg of theophylline were compression coated with various amounts of guar gum. The physical properties of the tablets were tested and in vitro release studies were performed. Samarium oxide (152-Sm) was added to the core tablet as the tracer. Scintigraphy was used to monitor the tablet's movement and distribution through the GI system of six healthy volunteers. In vivo scintigraphic studies showed that the tablets reached the colon at 5,6 and 8 h in three of the six subjects. Theophylline delivery to the terminal ileum or colon can be achieved and the theophylline-guar gum compression coated tablets may be a promising system for the treatment nocturnal asthma. But, more formulation work may be necessary for the determination of the exact coating thickness and the development of optimum formulation. (C) 2016 Elsevier B.V. All rights reserved.

Fungal growth indoors is a common problem both in older and modern buildings. Numerous studies demonstrate a deterioration of asthma in environments with fungal growth but precise estimates of exposure levels have not been reported. This study was carried out to investigate whether levels of airborne fungi were higher in homes of subjects with nocturnal asthma as compared to controls. Subjects with nocturnal asthma (n = 42) and non-nocturnal asthma (n = 14) were recruited from an outpatient department. Subjects without disease or respiratory symptoms (n = 24) served as controls. Among the asthmatics, determinations were made of pulmonary function before and after treatment with bronchodilatators. The subjects were equipped with a pump and a filter and instructed to sample air in their bedroom. The filters were analysed for the content of N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass. In some houses the number of colony forming units was also determined. Patients with asthma had significantly higher activities of NAHA in their bedrooms as compared to controls (31.2 vs. 12.5 U m−3, p = 0.004). When the material was divided according to the 2nd quartile of NAHA (14.0 U m−3), 29 out of 42 subjects with nocturnal asthma had high values compared to 5 out of 24 for the controls (p

Inhalation of hypertonic saline (HS) causes bronchoconstriction in asthmatic subjects. Repeated inhalation of HS leads to substantially reduced bronchoconstriction, known as the refractory period. Refractoriness due to different stimuli has also been described (cross-refractoriness). Nocturnal asthma is defined as an increase in symptoms, need for medication, airway responsiveness, and/or worsening of lung function that usually occurs from 4 to 6 am. Our objective was to determine the effect of refractoriness on nocturnal asthma. The challenge test consisted of inhalations of 4.5% saline with increasing durations until a reduction of 20% in forced expiratory volume in 1 s (FEV1) (PD20HS) or total time of 15.5 min. Twelve subjects with nocturnal asthma were challenged with HS at 16:00 and 18:00 h and FEV1 was measured at 4:00 h. One to 2 weeks later, FEV1 was determined at 16:00 and 4:00 h. LogPD20HS at 18:00 h was significantly greater than logPD20HS at 16:00 h, 0.51 +/- 0.50 and 0.69 +/- 0.60 mg, respectively (P = 0.0033). When subjects underwent two HS challenges in the afternoon, mean (+/- SD) FEV1 reduction was 206 +/- 414 mL or 9.81 +/- 17.42%. On the control day (without challenge in the afternoon) FEV1 reduction was 523 +/- 308 mL or 22.75 +/- 15.40% (P = 0.021). Baseline FEV1 values did not differ significantly between the control and study days, 2.48 +/- 0.62 and 2.36 +/- 0.46 L, respectively. The refractory period following HS challenges reduces the nocturnal worsening of asthma. This new concept may provide beneficial applications to asthmatic patients.

Individual differences in circadian rhythm have been studied since the past century. Chronotypes are a chronobiology classification based on the preferential times for beginning and ending activities throughout the day. Chronotypes can be classified as definitely morning, moderately morning, indifferent, moderately evening, and definitely evening. We aim to assess the distribution of chronotypes in asthmatics and the relationship of chronotype to the presence of nocturnal symptoms. Two hundred subjects were evaluated, 100 asthmatics and 100 non-asthmatics. The Morningness/Eveningness questionnaire was applied for chronotype determination. The asthmatics were subdivided according to the presence or absence of nocturnal symptoms. The chronotype distribution did not differ significantly between asthmatics and non-asthmatics. Thirty-five percent of the asthma group reported nocturnal symptoms. There was a significant difference in chronotype distribution between asthmatics with and without nocturnal worsening. The asthmatics with nocturnal symptoms had a lower prevalence of morning types and had a greater predominance of indifferent chronotype compared to asthmatics without nocturnal symptoms (p = 0.011). In conclusion, asthmatics with nocturnal symptoms present deviation from the chronotype distribution curve when compared to asthmatics without nocturnal symptoms. This is the first study to show the effect of a disease on chronotypes.

A time dependent pulsed release system consisting of an effervescent core surrounded by consecutive layers of swelling and rupturable polymers was prepared and evaluated. The cores containing salbutamol sulphate as bioactive agent were prepared by direct compression method using different ratios of microcrystalline cellulose and effervescent agent and then coated sequentially with an inner swelling layer containing a hydrocolloid, hydroxypropylmethylcellulose E5 and an outer rupturable layer having Eudragit RL/RS (1:1). The effects of various processing and formulative parameters on the performance of system were studied. The rupture and dissolution tests were studied using the USP paddle method at 50 rpm in 0.1 N HCl and phosphate buffer pH 6.8. The lag time of the drug release decreased by increasing the inner swelling layer and increased by increasing the rupturing layer level. All the results obtained in the present study suggest that osmotic pumping effect was involved which eventually lead to the drug release.

Nocturnal asthma is defined by a drop in forced expiratory volume in 1 second (FEV1) of at least 15% between bedtime and awakening in patients with clinical and physiologic evidence of asthma. Nocturnal asthma is associated with a circadian pattern in lung function, distal airway inflammation, glucocorticoid receptor affinity, pulmonary capillary blood volume, and beta-2 adrenergic receptor function may also contribute. Knowledge of these characteristics, along with an understanding of the specific therapies directed at the circadian nature of this disease, can result in significant improvements in lung function, sleep quality, and asthma related quality of life.&nbsp

Nachtliche und fruhmorgendliche respiratorische Beschwerden sind bei Patienten mit Asthma bronchiale sehr haufig zu finden. Es erscheint einleuchtend, wenngleich auch nicht ausreichend bewiesen, dass ein nachtliches Asthma mit Atemwegsobstruktion und Husten zu einer Storung der Schlafqualitat fuhren kann. Um einen kausalen Zusammenhang zwischen nachtlichem Asthma bronchiale und Schlaf herstellen zu konnen, mussen objektive Methoden herangezogen werden. Die nachtliche akustische Langzeitregistrierung von Wheezing und Husten stellt eine methodische Voraussetzung dar um klinische Zeichen des Asthma bronchiale im Zeitverlauf zu erfassen. Das zusatzliche Wissen uber den Zusammenhang zwischen nachtlichem Asthma bronchiale und Schlaf birgt Moglichkeiten fur neue therapeutische Konzepte. Im vorliegenden Artikel werden der aktuelle Wissensstand zum Einfluss von Asthma bronchiale auf den Schlaf sowie ungekehrt die Auswirkungen des Schlafs auf den Schweregrad der nachtlichen Bronchialobstruktionen zusammengefasst. Ebenso werden die aktuellen Methoden zur Erfassung der diagnostischen Parameter dargestellt.

The mechanisms of nocturnal asthma are intimately related to circadian rhythms, which influence inflammatory cells and mediators, hormone levels and cholinergic tone. Nocturnal airway narrowing in asthma is sometimes associated with steep disorders, such as obstructive sleep apnea syndrome (OSAS). The aims of this study were to evaluate the association of nocturnal asthma and OSAS, and investigate the influence of continuous positive airway pressure (CPAP) therapy to improve nighttime symptoms in asthmatic patients with OSAS. Forty-three asthmatic patients who had nocturnal symptoms in spite of the optimal medical treatment according to the Global Initiative for Asthma guidelines and associated with snoring were studied. Pulmonary function tests (PFTs), asthma nighttime symptom scores, and polysomnography were performed on all patients. We treated the patients with an apnea-hypopnea index (AHI) >= 15 (moderate-severe OSAS) (n = 16) with CPAP during 2 months. After 2 months, PFT, asthma nighttime symptom scores were reperformed. There was no significant difference in PFT values before and after CPAP treatment in OSAS patients. Asthma nighttime symptom scores were improved significantly (P < 0.05) after CPAP treatment. In conclusion, in some patients with nocturnal asthma, OSAS may be responsible disease for nocturnal symptoms. In this condition, CPAP improves nocturnal symptoms without amelioration in PFT abnormalities. (c) 2004 Elsevier Ltd. All rights reserved.

Background: Asthma is a chronic disease characterized by repeated attacks of breathlessness and wheezing, which occurs principally during night. This is due to circadian changes in ventilation and airway responsiveness. Hence, the chronomodulated therapy is more considering in the treatment of nocturnal asthma. Objective: The objective of the study was to prepare microcapsule‑based chronomodulated drug delivery system of montelukast sodium (MLS) for the treatment of nocturnal asthma. Materials and Methods: Five batches of MLS microcapsules were prepared using pH‑dependent polymer combination of Eudragit® S‑100 with L‑100. The optimized batch microcapsules were enclosed in a capsule to obtain chronomodulated pulsincap systems (CMPSs). In this system, natural gums were used as hydrogel plugs to achieve the required time lag. Microcapsules and CMPSs have been evaluated for their characteristic properties. Results: The developed microcapsules are spherical in shape with smooth surfaces. In vitro release studies predicted that M4 and M5 batches could control the drug release for a period of 12 h. The optimized batch microcapsules (M4) were used in the preparation of CMPSs. The natural hydrogel plugs, i.e. xanthan gum, gum kondagogu, and guargum used in CMPSs showed approximate lag phase of 5, 6, and 5.5 h and drug releases up to 16, 24, and 24 h, respectively. Conclusion: CMPSs containing Eudragit® microcapsules of MLS with programmable lag phase and prolonged drug release were successfully developed using natural gums as hydrogel plugs, which congregates the demands of chronomodulated therapy in asthma.

Asthma continues to be a global health problem, despite advances in diagnostic techniques and treatment. The inflammatory nature of asthma is currently indisputable, as is the involvement of the entire respiratory tree, both the proximal and most distal airways, which has been demonstrated in multiple studies. The development of the therapeutic arsenal, with more potent drugs and improved inhalation devices, has allowed a certain control to be maintained over the inflammatory process, although the inability to reach the most distal points of the airways has posed a stumbling block that seems difficult to overcome. However, the available information on the real role of distal airway involvement in asthma remains very scarce. Physiopathological evidence shows that, in addition to the large airways, the small or distal airways (those with a diameter of less than 2 mm) substantially contribute to the severity of asthma. Several studies have shown that the inflammatory process seems to be more intense in this area. This finding has been related to nocturnal asthma and an increase in glucocorticoid receptor-beta-expressing cells, associated with corticosteroid-resistant asthma and fatal asthma. Equally, small airway involvement seems to be a highly important factor in asthma in the pediatric age group.

The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening.For this purpose a double-blind, randomized, parallel group study was initiated in which 209 asthmatic patients (forced expiratory volume in one second=50–90% predicted) inhaled either 200 µg ciclesonide in the morning or in the evening, for 8 weeks. Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow (PEF), symptoms and use of rescue medication. The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis.Ciclesonide significantly improved asthma control. Morning and evening administration was shown to be equally effective for the different spirometry variables, evening PEF, symptoms, use of rescue medication and number of asthma exacerbations. Regarding morning PEF, the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated. No relevant influence on cortisol excretion was found.Overall, the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients' preference and individual medical needs, although evening administration may lead to a more pronounced improvement in morning peak expiratory flow.

We investigated changes in the circadian rhythm of peak expiratory flow (PEF) in seven persons with nocturnal asthma for a 24h span when (1) they were symptom free and their disease was stable, (2) their asthma deteriorated and nocturnal symptoms were frequent, and (3) they were treated with theophylline chronotherapy. Subjects recorded their PEF every 4h between 07:00 and 23:00 one day each period. Circadian rhythms in PEF were assessed using the group-mean cosinor method. The circadian rhythm in PEF varied according to asthma severity. Significant circadian rhythms in PEF were detected during the period when asthma was stable and when it was unstable and nocturnal symptoms were frequent. When nocturnal symptoms were present, the bathyphase (trough time) of the PEF rhythm narrowed to around 04:00; during this time of unstable asthma, the amplitude of the PEF pattern increased 3.9-fold compared to the symptom-free peiiod. No significant group circadian rhythm was detected during theophylline chronotherapy. Evening theophylline chronotherapy proved to be prophylactic for persons whose symptoms before treatment had occurred between midnight and early morning. Changes in the characteristics of the circadian rhythm of PEF, particularly amplitude and time of bathyphase, proved useful in determining when to institute theophylline chronotherapy to avert nocturnal asthma symptoms.

We studied circadian variation in FVC, FEV1, PEF, TLC, VC, and RV between 9:00 A.M. and 9:00 P.M. and analyzed how this variation affected estimated longitudinal change. Data from 876 adults were obtained in a longitudinal survey of samples from two Dutch areas. Subjects participated in four surveys held at 3-yr intervals between 1975 and 1985. FVC, FEV1, PEF, and VC increased from 9:00 A.M. until noon and decreased afterwards. TLC was constant over the day, whereas RV decreased from 9:00 A.M. to noon. Average variation in FVC, FEV1 and PEF, expressed as percentages of average level, was 4. 8% (200 ml), 2.8% (86 ml), and 3.1% (250 ml/s), respectively. These results are compatible with circadian changes in airway size. No differences in variability were found between men and women. Significantly larger changes between 9:00 A.M. and noon were found in young adults, smokers, and those with respiratory symptoms than in other subgroups. Adjustment for diurnal variation reduced, albeit slightly, residual standard deviations of estimated longitudinal declines. Average diurnal change was large relative to underlying longitudinal change. Its effect on longitudinal change within an individual can therefore be large depending on age, smoking habits, symptomatology, number of visits, time of measurement, and difference in time between measurements. However, when people are measured at random times during the day for at least three visits, or when measurements are made after 11:00 A.M., effects of diurnal variation in pulmonary function on estimated average longitudinal decline are minimal.

Asthma at night is characterized by a nocturnal increase in airway obstruction. It has been hypothesized that nocturnal asthma results from an increase in airway wall inflammation at night. However, studies on inflammatory cells in bronchoalveolar lavage (BAL) fluid and bronchial biopsies have produced conflicting data. This study assessed inflammatory cell numbers at 16:00 h and 04:00 h in bronchial biopsies of 13 healthy controls, 15 asthmatic patients with peak expiratory flow (PEF) variation < or =15% and 10 asthmatic patients with PEF variation >15%. There was no significant increase at night in the number of CD3, CD4, CD8, CD25, AAI (tryptase) and EG2-immunopositive cells in the submucosa in both groups. Numbers of EG2-positive cells in the two asthmatic groups were significantly higher than in healthy controls, both at 16:00 h (p15% than in asthmatics with PEF variation < or =15%. At 04:00 h the median numbers of EG2-positive cells (per mm basement membrane) in subjects with PEF variation >15% and < or =15% were 6 and 3 cells, respectively, and at 16:00 h 4 and 25 cells respectively. Increased nocturnal airway obstruction is not associated with increased numbers of inflammatory cells in the bronchial submucosa at night. Apparently, asthmatic patients with a peak expiratory flow variation >15% suffer from a higher overall severity of bronchial inflammation at night and during the day.

The purpose of this double-blind, randomised, placebo-controlled cross-over study was to evaluate whether corona ionisers placed in bedrooms could improve nocturnal asthma and other symptoms in asthmatics which might be related to the indoor climate. Active or inactive (placebo) ionisers were placed in the bedrooms of 15 patients for two subsequent 4-week periods. The patients recorded daily/nightly symptoms, medication and peak expiratory flow. A histamine challenge was performed initially and after each period to measure the effect on hyperresponsiveness. Statistical analysis showed no sig nificant differences between active and placebo periods with regard to lung function, medication, nocturnal asthma or other symptoms supposed to be related to indoor climate.

Feeding issues are prevalent in young children. Feeding will be defined here as the process of in‐ gesting food and drink in social environments where such activities take place. Estimates of problems may range from 13 to 50% in typically developing children, but may be as high as 80% in children with developmental disabilities [1-7]. In 1 to 10% of these children problems may be‐ come chronic and may affect their health and development [1, 8]. Anatomical, metabolic, gastro‐ intestinal, motor or sensory problems may be the cause of or may contribute to some of these feeding problems [8]. A global medical assessment is necessary when feeding problems persist, because some medical symptoms may not be recognized as associated with feeding at first sight, such as asthma. Even if the association remains unclear, a high prevalence of asthmatic children, particularly with nocturnal asthma, have gastro-esophageal reflux (GER) [9]. Both feeding and eating, the processing of food and drink in the mouth and swallowing, are also known as activi‐ ties of daily living (ADL) and studies examining the specific problems of children with Autism Spectrum Disorders (ASD), found that 46 to 89% have feeding problems [10-18].

Snoring was described in literature even before medicine. Common definitions do not consider acoustic measurements of snoring. In this paper we discuss the main pathophysiological aspects of snoring and the snoring-sleep relationship as the generating mechanisms. Snoring can be analysed and measured by the following methods: 1) Leq-Equivalent Continuous Sound Level, which only quantifies noisiness, annoyance, and damage to the partner's and snorer's hearing; 2) Power Spectrum, with frequency values, formantic structure data and typical shape, which can help to distinguish simple snoring from heavy snoring with obstructive sleep apnoea syndrome (OSAS); 3) Linear Prediction Code (LPC) method, which can define the cross-sectional area (CSA) of the upper airways and which locates sites of obstruction. Simulated snoring analysis with LPC and with simultaneous fluoroscopy permits the definition of CSA and the identification of three snoring patterns: nasal, oral and oronasal. Snoring is an important sign of sleep-related breathing disorders (SRBD), of the upper airway resistance syndrome (UARS), and of the OSAS. Snoring is a symptom of nasal obstruction and is associated with cardiovascular diseases and nocturnal asthma as a trigger or causative factor; however, its acoustic features in these disorders are not well-defined. Home monitoring of snoring is very useful for epidemiology and is mandatory, together with heart rate and arterial oxygen saturation (Sa,O2), to screen SRBD.

Purpose : To develop an oral capsule-based chronomodulated drug delivery system of salbutamol sulphate for the treatment of nocturnal asthma. Methods : The basic design of the proposed dosage form entails an insoluble cross-linked capsule body filled with drug-loaded pellets sealed with hydrocolloid plug and a soluble capsule cap. Various hydrocolloid polymers, namely, hydroxypropyl methylcellulose, (HPMC), hydroxypropyl cellulose (HPC), sodium alginate, polyethylene oxide (PEO) and guar gum. were used to optimize the plug material in the delivery in order to modulate lag period To avoid gastric transit time variability, the entire system was coated with Eudragit S100/Eudragit L100 dispersion (4:1), an enteric polymer system that dissolves at pH 6.8. Results : Time-specific pulsatile release with 4 h lag period was achieved with crosslinked insoluble gelatin capsule shells containing pellets prepared from Avicel PH 101/lactose (80: 10) and 3 % Acidisol as disintegrant. In vitro data indicate that the developed pulsatile system released almost 98 % of the drug shoertly after the predetermined lag time of 4 h. Conclusion : The developed system is capable of releasing the drug after a 4-h lag period. However, in vivo studies need to be carried out to ascertain the effectiveness of the formulation. Keywords : Time controlled, pH-controlled, Lag time, pulsed release, Hydrocolloid plug, Nocturnal asthma

Greater child daily global stress was associated with increased likelihood of awakening from asthma that night. Asthma awakenings were followed by greater morbidity the next day.

Objectives We sought to compare the characteristics of patients with asthma presenting to the emergency department (ED) during the night-time with those of patients presenting at other times of the day, and to determine whether the time of ED presentation is associated with the risk of hospitalisation. Design and setting A multicentre chart review study of 23 EDs across Japan. Participants Patients aged 18–54 years with a history of physician-diagnosed asthma, presented to the ED between January 2009 and December 2011 Outcome measures The outcome of interest was hospitalisation, including admissions to an observation unit, inpatient unit and intensive care unit. Results Among the 1354 patients (30.1% in the night-time group vs 69.9% in the other time group) included in this study, the median age was 34 years and ∼40% were male. Overall 145 patients (10.7%) were hospitalised. Patients in the night-time group were more likely to have a shorter duration of symptoms (≤3 hours) before ED presentation than those in the other time group (25.9% in night-time vs 13.4% in other times; p0.05). Similarly, the risk of hospitalisation did not differ between the two groups (11.3% in night-time vs 10.5% in other times; p=0.65). In a multivariable model adjusting for potential confounders, the risk of hospitalisation in the night-time group was not statistically different from the other time group (OR, 1.10; 95% CI 0.74 to 1.61; p=0.63). Conclusions This multicentre study in Japan demonstrated no significant difference in the risk of hospitalisations according to the time of ED presentation.

Preview More than two thirds of all patients with asthma struggle with nocturnal worsening of their symptoms, exercise-induced bronchoconstriction, or both. Understanding the causes of these problems provides a basis for controlling symptoms. Drs Wright and Martin elucidate those causes and make practical recommendations for minimizing nocturnal asthma and increasing patients' ability to exercise.

Resume La farine de sarrasin est un trophallergene puissant. La sensibilisation survient habituellement par ingestion, mais aussi par inhalation au cours d’expositions professionnelles ou domestiques. Les oreillers contenant des cosses de sarrasin peuvent etre contamines par la farine de sarrasin au cours de leur fabrication et representer une cause d’asthme nocturne chez les individus sensibilises au sarrasin.