Respiratory Airway Disease Research Articles

Effect of withdrawal of fusafungine from the market on prescribing of antibiotics and other alternative treatments in Germany: a pharmacovigilance impact study

PurposeKnowledge on unintended consequences of product withdrawals is limited. Fusafungine, indicated for treatment of upper respiratory airways disease (URAD), was withdrawn in the EU on May 28, 2016. Given concerns about possible substitution with antibiotics, this study aimed to assess the impact of the withdrawal of fusafungine on prescribing of antibiotics and other treatments.MethodsThe study was conducted using data from general practitioner (GP) and ear, nose and throat (ENT) practices in IMS® Disease Analyzer Germany. The quarterly prevalence of fusafungine prescribing was analysed for consultations involving the most common URAD between May 29, 2013 and May 28, 2017 in regular fusafungine-prescribing practices. Trends in the quarterly prevalence of antibiotics (AB), other nasal or throat preparations (N&T) and tyrothricin were analyzed. Practices with no fusafungine prescribing during the study served as controls. Changes in prescribing trend were evaluated using interrupted time series regression analysis.ResultsIn fusafungine-prescribing practices, withdrawal of fusafungine was associated with an immediate increase in prescribing of other N&Ts among patients consulting for URAD (+ 6.4%, 95% CI 2.3–10.5% in GP practices and + 9.0%, 95% CI 5.5–12.5% in ENT practices). There was no increase in antibiotic prescribing. In ENT practices; a small transient increase in tyrothricin prescribing occurred. No changes were seen in non-fusafungine-prescribing practices.ConclusionsWithdrawal of fusafungine was not associated with increased prescribing of antibiotics but was associated with increased prescribing of other N&Ts. The unintended impact of substitution to other treatments should be considered routinely when products are withdrawn or restricted in other ways.

Cytological Analysis of Tracheal Washing and Bronchoalveolar Lavage Fluid Obtained from Donkeys with Chronic Lung Disease

Pulmonary fibrosis, tracheal collapse and bronchoalveolar diseases belong to the most common causes of donkey deaths. The cytological analysis of tracheal washing (TW) and bronchoalveolar lavage fluid (BALF) have been proven in as useful tools for the investigation of lower respiratory airway diseases. Little is known about collection and analysis of TW and BALF in donkeys. The current study aimed at cytological analysis of TW and BALF in healthy donkeys and donkeys with chronic lung disease. TW and BALF fluid were collected from seventeen donkeys (five healthy and twelve affected with chronic lung disease) and were analysed for their cytological composition. In comparison to many other veterinary species, the percentage of eosinophils in TW and BALF was higher for both healthy and affected donkeys. The proportion of neutrophils in TW and BALF of affected donkeys was higher than that in control animals. The increase in the percentage of neutrophils and epithelial cells war higher in TW, when compared to BALF samples. Collectively, the comparative cytological analysis of TW and BALF samples from healthy and respiratory affected donkeys revealed that both TW and BALF could serve as helpful tools for the diagnosis of respiratory diseases in donkeys

High rates of respiratory symptoms and airway disease in mental health inpatients in a tertiary centre

People with severe mental illness (SMI) have a lower life expectancy due in part to a higher prevalence of cardiac and metabolic disease. Less is known of the prevalence of respiratory disease in this group. This cross-sectional, observational study aimed to assess the prevalence of symptoms associated with respiratory disease in patients admitted to an inpatient mental health unit. A convenience sample of 82 inpatients had a structured interview and questionnaire completed. The questionnaire included self-reported diagnoses of common diseases and screening questions designed to detect respiratory disease and sleep disordered breathing. Targeted spirometry was performed on the basis of symptoms and smoking status. Patients reported high rates of respiratory symptoms, including wheezing (38%) and dyspnoea (44%); 52% of patients reported daily tobacco use. Productive cough was significantly associated with tobacco use (P < 0.005). Ten patients (18%) had spirometry consistent with chronic obstructive pulmonary disease (COPD) of whom six did not have a formal diagnosis of COPD previously. People with SMI have high rates of respiratory symptoms with a high prevalence of COPD on spirometry. Half of the COPD cases were not previously diagnosed, suggesting a hidden burden of respiratory disease in patients with SMI.

Is recurrent respiratory infection associated with allergic respiratory disease?

ABSTRACTObjective: Respiratory infections cause high morbidity and mortality worldwide. This study aims to estimate the relationship between allergic respiratory diseases with the occurrence of recurrent respiratory infection (RRI) in children and adolescents. Methods: The International Study of Asthma and Allergies in Childhood questionnaire and a questionnaire that provides data on the history of respiratory infections and the use of antibiotics were used to obtain data from patients. The relationship between the presence of asthma or allergic rhinitis and the occurrence of respiratory infections in childhood was analyzed. Results: We interviewed the caregivers of 531 children aged 0 to 15 years. The average age of participants was 7.43 years, with females accounting for 52.2%. This study found significant relationship between: presence of asthma or allergic rhinitis with RRI, with prevalence ratio (PR) of 2.47 (1.51–4.02) and 1.61 (1.34–1.93), respectively; respiratory allergies with use of antibiotics for respiratory problems, with PR of 5.32 (2.17–13.0) for asthma and of 1.64 (1.29–2.09) for allergic rhinitis; asthma and allergic rhinitis with diseases of the lower respiratory airways, with PR of 7.82 (4.63–13.21) and 1.65 (1.38–1.96), respectively. In contrast, no relationship between upper respiratory airway diseases and asthma and allergic rhinitis was observed, with PR of 0.71 (0.35–1.48) and 1.30 (0.87–1.95), respectively. Conclusions: RRI is associated with previous atopic diseases, and these conditions should be considered when treating children.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD.

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.

Bronchial Thermoplasty by Application of Ultrasound Energy

Background: Asthma is a chronic inflammatory disease of respiratory airways, typically marked by spasms in the bronchi of the lungs, causing difficulty in breathing. Although the disease is very well documented, therapies are limited and patients mostly undergo symptom management. Bronchial thermoplasty is a radiofrequency-based treatment for severe asthma approved by Food and Drug Administration (FDA) in 2010 (Alair system, Boston Scientific Inc). Here we propose the use of ultrasound (US) energy to perform bronchial thermoplasty. Our hypothesis is that ultrasound affects bronchial smooth muscle at least as effective as radio-frequency (RF) but causes less collateral damage, and holds the potential to reduce the procedure time. In this publication we present a direct comparison of acute thermoplasty effects of RF energy versus ultrasound energy. Objective: To evaluate a bronchoscopic procedure based on circumferential ultrasound energy and its effect on bronchial wall structures in comparison to RF thermoplasty for asthma treatment. Methods: This is an observational study aiming for a direct comparison of an ultrasound system with existing asthma therapy based on radio-frequency. Mongrel dogs were used for optimization of ultrasound energy (300 J, 200 J, 100 J) with a 4.5 and 5.5 mm balloon catheter. 100 J was ultimately directly compared with RF effects on bronchial wall structures. Safety and efficacy of the ultrasound system was already previously established during renal denervation clinica stdies. Results: 12 mongrel dogs were used. Bronchoscopy procedures were feasible in all cases, and no adverse effects were seen in any dogs. Lungs were collected for histology and H&E staining. With the optimized 100 J ultrasound energy we observed mild bronchial tissue injury, with minimal hemorrhage and preservation of respiratory epithelium. The RF catheter caused distinct focal injury points resulting from direct contact of the RF electrodes with bronchial wall tissue. Acute histological examination shows hemorrhagic injury along the RF energy path with significant necrosis to all bronchial wall elements including respiratory epithelium. Conclusion: Ultrasound energy is safe, feasible, and at least as effective in affecting bronchoconstriction as RF energy offering a viable alternative to radiofrequency-based lung disease treatments.

Smoking cessation effectiveness in smokers with COPD and asthma under real life conditions

Although smoking cessation is strongly indicated by international guidelines as an effective therapeutic tool for patients with COPD and Asthma, a large proportion of them do not quit smoking and they are regarded as a "difficult" target group. To study the effectiveness of an intensive smoking cessation program in smokers with COPD and asthma under real-life conditions. 166 smokers with COPD, 120 smokers with asthma and 1854 control smokers attended the smoking cessation program in the out-patient patient Smoking Cessation Clinic of the Pulmonary Department in Athens University. Continuous Abstinence Rate (CAR) was evaluated in 3, 6, 9 and 12 months after the target quit date. Short-term CAR (in 3 months) was 49.4% for COPD smokers, 51.7% for asthmatic smokers and 48.0% for the control group of smokers. 12 months after the initial visit the CAR was 13.9%, 18.3% and 15.9%, respectively. No statistically significant differences between groups at any study period were found. Smokers with good compliance with the program had higher long-term CAR after 12 months: 37.7% in COPD smokers, 40.0% in asthmatic smokers and 39.3% in control smokers. High CAR was observed at all stages of COPD severity. The results support the view that smokers with respiratory obstructive airway diseases of any severity should be offered an intensive smoking cessation program with regular and long-term follow-up. This will help them to achieve high abstinence rates and prevent relapses.

Associations between ambient air pollution and daily mortality among elderly persons in Montreal, Quebec

BackgroundPersons with underlying health conditions may be at higher risk for the short-term effects of air pollution. We have extended our original mortality time series study in Montreal, Quebec, among persons 65years of age and older, for an additional 10years (1990–2003) to assess whether these associations persisted and to investigate new health conditions. Methods and resultsWe created subgroups of subjects diagnosed with major health conditions one year before death using billing and prescription data from the Quebec Health Insurance Plan. We used parametric log-linear Poisson models within the distributed lag non-linear models framework, that were adjusted for long-term temporal trends and daily maximum temperature, for which we assessed associations with NO2, O3, CO, SO2, and particles with aerodynamic diameters 2.5μm in diameter or less (PM2.5). We found positive associations between daily non-accidental mortality and all air pollutants but O3 (e.g., for a cumulative effect over a 3-day lag, with a mean percent change (MPC) in daily mortality of 1.90% [95% confidence interval: 0.73, 3.08%] for an increase of the interquartile range (17.56μgm−3) of NO2). Positive associations were found amongst persons having cardiovascular disease (cumulative MPC for an increase equal to the interquartile range of NO2=2.67%), congestive heart failure (MPC=3.46%), atrial fibrillation (MPC=4.21%), diabetes (MPC=3.45%), and diabetes and cardiovascular disease (MPC=3.50%). Associations in the warm season were also found for acute and chronic coronary artery disease, hypertension, and cancer. There was no persuasive evidence to conclude that there were seasonal associations for cerebrovascular disease, acute lower respiratory disease (defined within 2months of death), airways disease, and diabetes and airways disease. ConclusionsThese data indicate that individuals with certain health conditions, especially those with diabetes and cardiovascular disease, hypertension, atrial fibrillation, and cancer, may be susceptible to the short-term effects of air pollution.

Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease.

Deleterious responses to pathogens during infancy may contribute to infection and associated asthma. Chlamydia respiratory infections in early life are common causes of pneumonia and lead to reduced lung function and asthma. We investigated the role of interleukin-13 (IL-13) in promoting early-life Chlamydia respiratory infection, infection-induced airway hyperresponsiveness (AHR), and severe allergic airway disease (AAD). Infected infant Il13(-/-) mice had reduced infection, inflammation, and mucus-secreting cell hyperplasia. Surprisingly, infection of wild-type (WT) mice did not increase IL-13 production but reduced IL-13Rα2 decoy receptor levels compared with sham-inoculated controls. Infection of WT but not Il13(-/-) mice induced persistent AHR. Infection and associated pathology were restored in infected Il13(-/-) mice by reconstitution with IL-13. Stat6(-/-) mice were also largely protected. Neutralization of IL-13 during infection prevented subsequent infection-induced severe AAD. Thus, early-life Chlamydia respiratory infection reduces IL-13Rα2 production, which may enhance the effects of constitutive IL-13 and promote more severe infection, persistent AHR, and AAD.

Sleep-disordered Breathing and Pneumonia

Research Article| September 01 2012 Sleep-disordered Breathing and Pneumonia AAP Grand Rounds (2012) 28 (3): 33. https://doi.org/10.1542/gr.28-3-33 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Sleep-disordered Breathing and Pneumonia. AAP Grand Rounds September 2012; 28 (3): 33. https://doi.org/10.1542/gr.28-3-33 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: pneumonia, sleep apnea syndromes Source: Goldbart AD, Asher T, Givon-Lavi N, et al. Sleep-disordered breathing is a risk factor for community-acquired alveolar pneumonia in early childhood. Chest. 2012; 141(5): 1210– 1215; doi: https://doi.org/10.1378/chest.11-1998Google Scholar To determine if sleep-disordered breathing (SDB) is more frequent among children with community-acquired alveolar pneumonia (CAAP), investigators from the Soroka and Ben-Gurion Universities in Israel conducted a case-control study in 2006 to 2008 of children <5 years old. Children who met World Health Organization (WHO) radiologic criteria for alveolar pneumonia1 were enrolled from the pediatric emergency department (ED) or after hospital admission. Age-matched controls were enrolled from well child clinic visits or admissions for elective surgery. Using a previously developed questionnaire,2 the authors interviewed parents of case and control children regarding symptoms of SDB in the preceding 12 months (including snoring >3 times a week, nighttime breathing problems, restless sleep, chronic rhinorrhea, and daytime tiredness or irritability), history of previous polysomnography (PSG) and/or adenoidectomy, and demographics. Of 2,645 children radiographically diagnosed with CAAP, 1,546 were enrolled. Compared to 441 controls, children with CAAP were significantly older (mean age of 22 months vs 11 months), more likely to have been born premature (12.9% vs 6.1%; P < .001), and less likely to have been breastfed (85.5% vs 95%). Symptoms of SDB were significantly more common among children with CAAP compared to control children, including snoring (18.6% vs 2.9%), restless sleep (16.8% vs 5.3%), rhinorrhea (12.5% vs 1.8%), and daytime tiredness or irritability (6.3% vs 0.2%). History of an adenoidectomy was also significantly more common among children with CAAP. Obstructive sleep apnea (OSA) had been confirmed by PSG before enrollment in 5% of the children with CAAP as compared to only 1.3% of controls (OR=3.7; 95% CI, 1.6–10.0). The authors conclude that SDB is an independent risk factor for CAAP and recommend that SDB be considered among young children with CAAP. Drs Dubik and Geskey have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. The association between SDB and lower respiratory airway diseases has been reported in adults and has been suspected among young children.1 Aspiration to some degree may be the underlying mechanism.2 However, there are a number of limitations in the current study that pediatricians should consider before screening every child who is diagnosed with pneumonia for SDB, especially if it would automatically lead to PSG. First, because of the design of the study, the investigators could not control for several potential confounders. There were significant differences between the case and control groups on several demographic characteristics; for instance, children with CAAP had higher rates of daycare attendance, were less likely to have been breastfed, and had higher rates of asthma and pneumonia than the control group. Second, laboratory and clinical data were collected but were not extensively reported. This is important because even though the authors used a... You do not currently have access to this content.

Combined Haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma

Background20–30% of patients with asthma have neutrophilic airway inflammation and reduced responsiveness to steroid therapy. They often have chronic airway bacterial colonisation and Haemophilus influenzae is one of the most...

Anti-inflammatory effects of garenoxacin on IL-8 production and ERK1/2 activation induced by lipopolysaccharides in A549 and THP-1 cells

The anti-inflammatory properties of macrolides have been applied to the treatment of inflammatory airway diseases. Although the anti-inflammatory properties of fluoroquinolones have been reported, no reports are available regarding a newly developed fluoroquinolone, garenoxacin (GRNX). To examine the immunomodulatory effect of GRNX, we examined the transcription and secretion of inflammatory cytokines by human airway epithelial cells and monocytes stimulated with lipopolysaccharide (LPS). A human lung epithelial cell line (A549) and a human monocyte cell line (THP-1) were stimulated with LPS and exposed to different concentrations of GRNX. The transcription and secretion of interleukin 8 (IL-8) in both A549 and THP-1 cells was measured by real-time PCR and an enzyme-linked immunosorbent assay, respectively. Treatment with GRNX significantly inhibited the transcription and secretion of IL-8 induced by LPS-stimulated cells through inhibitory ERK1/2 phosphorylation. GRNX has anti-inflammatory activity through its capacity to alter the secretion of IL-8 from A549 and THP-1 cell lines. Our findings suggest that GRNX is suitable for the treatment of LPS-induced respiratory infection and inflammatory airway diseases.

Interactive Effects of Antioxidant Genes and Air Pollution on Respiratory Function and Airway Disease: A HuGE Review

Susceptibility to the respiratory effects of air pollution varies between individuals. Although some evidence suggests higher susceptibility for subjects carrying variants of antioxidant genes, findings from gene-pollution interaction studies conflict in terms of the presence and direction of interactions. The authors conducted a systematic review on antioxidant gene-pollution interactions which included 15 studies, with 12 supporting the presence of interactions. For the glutathione S-transferase M1 gene (GSTM1) (n=10 studies), only 1 study found interaction with the null genotype alone, although 5 observed interactions when GSTM1 was evaluated jointly with other genes (mainly NAD(P)H dehydrogenase [quinone] 1 (NQO1)). All studies on the glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism (n=11) provided some evidence of interaction, but findings conflicted in terms of risk allele. Results were negative for glutathione S-transferase T1 (GSTT1) (n=3) and positive for heme oxygenase 1 (HMOX-1) (n=2). Meta-analysis could not be performed because there were insufficient data available for any specific gene-pollutant-outcome combination. Overall the evidence supports the presence of gene-pollution interactions, although which pollutant interacts with which gene is unclear. However, issues regarding multiple testing, selective reporting, and publication bias raise the possibility of false-positive findings. Larger studies with greater accuracy of pollution assessment and improved quality of conduct and reporting are required.

Aeroallergen Sensitization in Children with Allergic Rhinitis: Prevalence and Risk Associations

Aeroallergen Sensitization in Children with Allergic Rhinitis: Prevalence and Risk Associations

Uso de corticosteroide na síndrome do desconforto respiratório agudo em pacientes pediátricos

The use of corticosteroids in acute lung injury and acute respiratory distress syndrome is one of the most controversial issues in the literature. However, acute lung injury/acute respiratory distress syndrome studies are restricted to adults, despite the widespread use of corticosteroid for hyper-reactive respiratory airway diseases in children. This review aimed to describe experimental and clinical evidence for corticosteroid therapy in acute lung injury/acute respiratory distress syndrome and to point out the risks and benefits of its use in pediatrics. For this purpose, an extensive review of the literature was performed from 1980 to 2010 including both experimental and clinical papers, as well as reviews and meta-analysis, using Medline, Cochrane Central Register of Controlled Trials, Cochrane database of systematic reviews, SciELO, Lilacs and Bireme databases. The search terms were: acute lung injury, acute respiratory distress syndrome, steroids, child, clinical trials, meta-analyses, reviews, and case reports. Most studies showed that the corticosteroids-induced down-regulation of systemic inflammatory response is associated with oxygenation improvement, reduction of multiple organ dysfunctions, mechanical ventilation time, and intensive care units length of stay. Based on the literature, the authors suggest early and prolonged methylprednisolone administration for acute lung injury/acute respiratory distress syndrome, using continuous 1 mg/kg/day infusion to prevent glycemic variability, associated with strict infection surveillance. In addition, they recommend some diagnostic parameters, interventions and choices of endpoint variables to be adjusted to improve pediatric trials feasibility. Therefore, more research is required to establish the safety and efficacy of methylprednisolone in pediatric patients with acute lung injury/acute respiratory distress syndrome , as well as to determine the best parameters for monitoring steroid side effects and outcomes.

Physiological measurements and prevalence of lower airway diseases in Trotters with dorsal displacement of the soft palate

Dorsal displacement of the soft palate (DDSP) is one of the most common obstructive conditions of the upper respiratory tract in the racehorse. This condition has a complex aetiology which may be caused or exacerbated by pharyngeal inflammation. Additionally, lower respiratory airway diseases may be associated with DDSP thereby contributing to exercise intolerance in these horses. The aim of this study was to measure physiological variables during a standardised exercise test and to assess the prevalence and consequences of lower respiratory airway disease in horses with DDSP. A total of 46 horses were included in this study: 22 in the control and 24 in the DDSP groups. All horses performed a SET with measurement of heart rate (HR) and blood lactate concentration. One hour post exercise, respiratory samples were collected for cytological and bacteriological analysis. During exercise, the DDSP group had higher blood lactate concentration than the control group. According to BAL results, 50 and 63% of control and DDSP group horses, respectively, had evidence of inflammatory airway disease (IAD). In the DDSP group, 42% of horses had a syndrome of tracheal inflammation (STI) with 71% of this group having bacteria isolated at >10(5) CFU/ml. Horses with DDSP showed evidence of a high prevalence of IAD and STI with an associated positive bacteriology in 55% of the cases. Even if DDSP is treated by surgery, the authors' recommendation would be to investigate the possibility of lower respiratory airway problems which may also be impacting the horse's performance and/or surgery efficiency.

Monthly variation of Dermatophagoides allergens and its influence on respiratory allergy in a high altitude environment (Quito, 2800 m a.s.l. in Andean Ecuador)

Background Seasonal variation of Dermatophagoides allergens and its influence in allergic respiratory airway diseases has not been investigated in Andean cities. The objective of this study was to evaluate those parameters in a city located in the Andean mountains. Methods Der p1 and Der f1 were measured in dust samples from mattresses in 13 houses in Quito (2800 m above sea level). Samples were collected monthly from August 2004 to July 2005. Patients presenting to a local outpatient allergy clinic with asthma and rhinitis and isolated allergy to Dermatophagoides were analysed to determine if a correlation existed between seasonal Der allergen levels and the number of patients presenting with allergies. Results High levels of dust mites and humidity were observed throughout the year. The highest geometrical mean values of allergens were detected in April ( Der p1, 10.15 μg/g) and May ( Der f1, 13.03 μg/g), whilst the lowest levels were detected in August (Der p1, 4.26 μg/g), and September (Der f1, 1.4 μg/g). Of the 361 patients examined, 182 were allergic to Dermatophagoides, (45.6% asthmatics, 97.8% rhinitics, and 43.4% with both diseases). Patient presentation spiked in August, and from February to May. However, there was not a significant correlation between mite allergen concentrations and humidity or the number of patients presenting with allergies. Conclusions Dust samples from mattresses in Quito revealed high concentrations of Der p1 and Der f1. We observed a trend towards increased presentation of asthmatic and rhinitic patients in the months with highest levels of allergens.

The non‐proteolytic house dust mite allergen Der p 2 induce NF‐κB and MAPK dependent activation of bronchial epithelial cells

House dust mites (HDM) are well-known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro-inflammatory mediators, while there is limited knowledge regarding such activity among non-proteolytic HDM allergens. To investigate whether Der p 2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation. The human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was studied using specific inhibitors. Der p 2 activated bronchial BEAS-2B and NHBE cells, but not alveolar A549 cells. In BEAS-2B cells Der p 2 induced dose-dependent up-regulation in both mRNA level and protein secretion of granulocyte-macrophage colony-stimulating factor, IL-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3alpha. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)-1 was also up-regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF-kappaB and MAPK activation in different ways, while expression of ICAM-1 was solely dependent on NF-kappaB activation. These results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium.

Kampo Medicine in the Treatment of Respiratory Airway Diseases

本論文では漢方医学的と同時に西洋医学的観点から，気道系領域疾患の治療として，西洋薬とともにどのように漢方薬を使用するかを考察した。漢方治療では一般的に患者の体力，病態，病気の進展に合わせて薬方を決定することが重要である。喀痰がからまるという患者の病態が去痰薬，気管支拡張薬，吸入ステロイド薬，抗菌薬では十分に改善しない場合，例えば半夏厚朴湯という漢方薬は喀痰がほとんどなく，咽頭部の閉塞感を訴える場合に効果が期待できる。咳嗽反射，嚥下反射の低下は誤嚥性肺炎の誘因になりうる。そのような場合，半夏厚朴湯の投与は咳嗽反射，嚥下反射を改善することにより，誤嚥性肺炎を予防しうる。遷延性あるいは慢性咳嗽は鎮咳薬，抗菌薬，去痰薬，気管支拡張薬，吸入ステロイド薬などの西洋薬を使用しても，十分に改善しない場合がある。麦門冬湯，五虎湯，麻杏甘石湯，越婢加半夏湯などの漢方薬は，そのような場合に有用である可能性がある。西洋医学の薬と漢方薬の併用は，新たな効果を発揮しうると期待する。

Role of respiratory viral infections in the development of atopic conditions

Respiratory viral infections are implicated in both protection from, and inception of, allergic airway disease. Severe lower respiratory tract viral infections are associated with recurrent wheeze, asthma and atopy. It is unclear if this association is causal and the underlying mechanisms governing this are unknown. Whilst respiratory viral infections are the major precipitants of acute exacerbations of wheezing illness, early life infections are also clearly associated with protection from allergic diseases. This article aims to review the current understanding of the complex relationship between lower respiratory tract viral infections and their impact upon development of atopy in the airway. Clinical studies and animal models have further demonstrated that lower respiratory tract viral infections are strongly associated with development of recurrent wheeze and asthma with human rhinoviruses being shown to be the most prevalent cause of lower respiratory tract viral infections in infants, along with associated asthma development. A case-control study provided evidence of a contributory role for respiratory viral infections within this association, whilst recent experimental studies provide a possible mechanistic insight. Progress into understanding the relationship between respiratory viral infections and allergic airway disease is essential for development of treatments aimed at treating common risk factors mediating association but not cause. Recent findings may have begun to identify key pathways open to therapeutic intervention.