Inhaler Steroid Use Changes Oral and Airway Bacterial and Fungal Microbiome Profile in Asthma Patients.

INTRODUCTION: The full spectrum of bacterial and fungal species in adult asthma and the effect of inhaled corticosteroid use is not well described. The aim was to collect mouthwash and induced sputum samples from newly diagnosed asthma patients in the pretreatment period and in chronic asthma patients while undergoing regular maintenance inhaled corticosteroid therapy, in order to demonstrate the bacterial and fungal microbiome profile. METHODS: The study included 28 asthmatic patients on inhaler steroid therapy, 25 steroid-naive asthmatics, and 24 healthy controls. Genomic DNA was isolated from induced sputum and mouthwash samples. Analyses were performed using bacterial primers selected from the 16S rRNA region for the bacterial genome and "panfungal" primers selected from the 5.8S rRNA region for the fungal genome. RESULTS: Dominant genera in mouthwash samples of steroid-naive asthmatics were Neisseria, Haemophilus, and Rothia. The oral microbiota of asthmatic patients on inhaler steroid treatment included Neisseria, Rothia, and Veillonella species. Abundant genera in induced sputum samples of steroid-naive asthma patients were Actinomyces, Granulicatella, Fusobacterium, Peptostreptococcus, and Atopobium. Sputum microbiota of asthma patients taking inhaler steroids were dominated by Prevotella and Porphyromonas. Mucor plumbeus and Malassezia restricta species were abundant in the airways of steroid-naive asthma patients. Choanephora infundibulifera and Malassezia restricta became dominant in asthma patients taking inhaled steroids. CONCLUSION: The oral and airway microbiota consist of different bacterial and fungal communities in healthy and asthmatic patients. Inhaler steroid use may influence the composition of the oral and airway microbiota.

Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

BACKGROUND: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. OBJECTIVE: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. METHODS: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. RESULTS: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). CONCLUSION: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.

Contribution of neurogenic and allergic ways to the pathophysiology of nonallergic rhinitis.

BACKGROUND: A neuroallergic interaction was reported in the pathogenesis of allergic rhinitis (AR), but the pathophysiology of nonallergic rhinitis (NAR) is poorly understood. We aimed to explore the contribution of neuroallergic mechanisms to the pathogenesis of NAR. METHODS: Subjects were divided into three groups - NAR patients (n = 25), AR patients (n = 16) and the control group (n = 10) - and were assessed using the nasal provocation test (NPT) with house dust mite. Total symptom scores, nasal inspiratory peak flow and nasal lavage were performed before and after NPT. Nasal brushing and scraping was done after NPT. RESULTS: NPT was positive in NAR (52%) and AR (100%) patients and negative in all controls. After NPT, total symptom scores increased in both rhinitis groups. Post-NPT values of nasal inspiratory peak flow decreased only in AR patients. NAR patients showed a similar inflammatory cell profile in the nasal smears to AR patients which was different in controls. There were more tryptase- and immunoglobulin E (IgE)-positive cells in the nasal mucosa of AR patients, and more substance-p-positive cells were observed in NAR patients compared with controls. However, IgE- and tryptase-positive cells in NAR patients and substance-p-positive cells in AR patients were detectable in nasal mucosa, but rarely in the controls. Comparing the values before and after NPT, tryptase significantly increased in the nasal lavages of AR and NAR patients, while house dust mite-specific IgE did not change. CONCLUSIONS: We showed the existence of a common pathophysiological mechanism with different contributions in AR and NAR. We conclude that the difference in dominance of neuroallergic ways may determine the major phenotype of rhinitis.

The role of CD14 gene promoter polymorphism in tuberculosis susceptibility.

BACKGROUND: CD14 is expressed principally by cells of monocyte/macrophage lineage and plays a pivotal role in the innate immunity to intracellular infections. Recent research findings have revealed an association between the CD14 gene promoter polymorphism and several major infectious diseases. OBJECTIVE: The aim of the present study was to investigate the association between the CD14-159C/T polymorphism and tuberculosis in a Turkish population. METHODS: For this purpose, 88 consecutive patients with tuberculosis (63 pulmonary, 25 extrapulmonary) and 116 control subjects were enrolled into a prospective study. We determined CD14-159 genotypes by polymerase chain reaction - restriction fragment length polymorphism analysis and also measured serum concentrations of soluble CD14 (sCD14) by using a quantitative sandwich enzyme immunoassay technique. RESULTS: There was no significant difference in terms of genotype distribution between patients with tuberculosis (CC 18.2%, CT 48.9%, TT 33.0%) and controls (CC 12.9%, CT 50.9%, TT 36.2%) or between patients with pulmonary and extrapulmonary tuberculosis. Serum levels of sCD14 were significantly increased in patients with active tuberculosis compared to those with inactive tuberculosis and healthy controls (p<0.001). However, levels of sCD14 were not associated with any genotypes of CD14-159. CONCLUSION: The genotyping findings of the present study do not support a role for the CD14-159C/T polymorphism in the development of tuberculosis, at least in the geographical region of central Anatolia. Significantly elevated serum sCD14 levels in patients with active disease reflect the importance of the mononuclear phagocytic system activation in tuberculosis.

Efficacy and safety of H1-antihistamines: an update.

H1-antihistamines are inverse agonists that combine with and stabilize inactive conformation of H1-receptors. Thus they interfere with actions of histamine at H1-receptors. They are widely used for treatment of allergic rhinitis, allergic conjunctivitis, urticaria, coughs, colds and insomnia. H1-antihistamines are classified as older 'first generation' and newer 'second generation'. First generation H1-antihistamines have poor receptor H1-receptor selectivity, and cross blood-brain-barrier. They have a lot of adverse events such as anti-muscarinic, anti-α-adrenergic, anti-serotonin, and sedative effects. In contrast, second generation H1-antihistamines were highly selective for the histamine H1-receptor, do not cross the blood brain barrier, and have minimal adverse events. The risks of first-generation H1-antihistamines have been clearly underestimated, particularly when purchased as nonprescribed over the counter medications by public. This review summarizes current literature to evaluate antihistamines including their mechanism, indications and side-effects.

Disseminated tuberculosis with lymphatic, splenic and scrotal abscesses: a case report.

INTRODUCTION: Disseminated tuberculosis can involve several organs and clinically present with a potpourri of signs and symptoms. Early diagnosis and timely initiation of proper treatment are of great importance in preventing the later complications of the disease. CASE PRESENTATION: We report a case with disseminated tuberculosis who exhibited a wide spectrum of extrapulmonary involvement. The present case had lung and lymph node tuberculosis with abscess formation and remained undiagnosed for two years. Thereafter, multiple splenic abscesses developed that necessitated splenectomy, and at the final stage, he presented with scrotal abscesses. CONCLUSION: This paper highlights the diverse clinical appearances of disseminated tuberculosis and the significant importance of early diagnosis and treatment.

Perception of bronchoconstriction in obstructive pulmonary diseases (disease-specific dyspnoea).

The perception of dyspnoea differs between subjects with obstructive pulmonary diseases, partly because the underlying mechanisms for bronchoconstriction are different. We investigated the perception of bronchoconstriction in subjects with bronchiectasis, asthma and chronic bronchitis and possible contributing factors. Forty-seven non-smoking subjects with bronchiectasis, 50 subjects with asthma and 31 with chronic bronchitis were challenged with histamine. The Borg score was assessed before and after each challenge. The perception score corresponding to a fall in the forced expiratory volume in 1 s (FEV(1)) by 20% (PS(20)) was calculated. The mean values of DeltaBorg/DeltaFEV(1) (the Borg score change divided by the change in FEV(1) as a percentage of the baseline FEV(1)) and PS(20) of subjects with bronchiectasis and chronic bronchitis were significantly lower than in subjects with asthma after histamine challenge. The ratio of non-perceivers was higher in bronchiectasis (25.5%) and in chronic bronchitis (32.3%) than in asthma (4.0%). When all subjects were considered, DeltaBorg/DeltaFEV(1) values were significantly related to female sex ( r (2)=11.5%, P =0.0001), but not to age, duration of the disease, PD(20) or baseline FEV(1)%. The present study indicates that perception of histamine-induced bronchoconstriction is lower in patients with bronchiectasis and chronic bronchitis than in asthmatic patients, and that sex partially contributes to this difference.