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.

Characteristics of asthma in an older adult population according to sex and control level: why are asthma symptoms in older women not well-controlled?

OBJECTIVE: The older adult population in Turkey has increased by 22.6% in the last 5 years, and the characteristics of such patients with asthma remain uninvestigated. Therefore, we aimed to evaluate the characteristics of older adults with asthma according to sex and asthma control status to provide an in-depth overview of asthma in this population in Turkey. METHODS: The data of older adults (age 65 years and over) with asthma were obtained from a multicenter, cross-sectional asthma database registry (Turkish Adult Asthma Registry, TAAR) funded by the Turkish Thoracic Society. Comparisons were made based on sex and asthma control levels using the Global Initiative for Asthma (GINA) Asthma Symptom Control Questionnaire. RESULTS: Of the 2053 (11.5%) patients registered with the TAAR, 227 were older adults (median age, 69 (8), women, 75.8% (n = 172)). Of these, 46.5% (n = 101) had obesity to some degree. Compared with men, women had lower education, income levels, and employment rates. Additionally, women exhibited a higher prevalence of obesity, hypertension, and thyroid gland disease than men. Being female (OR: 2.99; 95% CI: 1.307-6.880), the presence of gastroesophageal reflux disease (OR: 2.855; 95% CI: 1.330-6.130), and a predicted forced expiratory volume in the first-second value lower than 80% (OR: 2.938; 95% CI: 1.451-5.948) were associated with poorly controlled asthma. CONCLUSIONS: Herein, older adults comprised 11.5% of adult patients with asthma. Being female poses a disadvantage in terms of both asthma prevalence and control in the older adult asthmatic population owing to the prevalence of comorbidities and socioeconomic sex-related distinguishing factors.

Functionality of natural killer cells in obese asthma phenotypes.

BACKGROUND: Obesity-associated asthma (OA) is a difficult to treat asthma phenotype due to its severity and poor response to inhaled steroids. Early-onset allergic (EoOA) and late-onset non-allergic (LoOA) OA are suggested subtypes of this phenotype. Natural Killer (NK) cells are key elements of innate immunity involved in cytotoxicity and immune regulation, with uncertain role in OA pathogenesis. METHODS: Early-onset allergic and LoOA patients together with obese non-asthmatic (ONA) controls have been enrolled in the study. Peripheral blood samples have been collected for analysis. Percentages of total NK cells, CD3- CD56dim and CD3- CD56bright NK cell subsets, cytotoxic activity, intracellular interferon-γ, interleukin (IL)-10, IL-13, IL-17 secretion and activatory receptors (NKG2D, NKp46i and NKp44) have been investigated by flow cytometry. The effect of IL-12 and IL-23 stimulation on NK cells and intracellular cytokines in different groups have also been analysed and compared with unstimulated conditions. RESULTS: Results of ONA (n = 5, age 42 ± 8), EoOA (n = 5, age 42 ± 10) and LoOA (n = 8, age 46 ± 8) patients have analysed. Body Mass Index has been found to be negatively correlated with CD69 (p = .022, r = -0.534). NKG2D receptor has been significantly low in CD56dim cells of asthma population (p = .046). NKp44 receptor expression has increased after IL-12 stimulation in EoOA and control group (p = .02). Intracellular IL-10 content has increased in LoOA and control subjects (p = .018, p = .03) but not in the EoOA group. Intracellular IL-17 level has found be higher in allergic OA group. LoOA patients showed a decreased NK cytotoxicity compared with the early-onset asthma group (p = .05). CONCLUSION: Our study suggests an impaired NK receptor expression, activation and reduced cytotoxicity in OA patients together with variances between different subtypes of this phenotype. This data would be beneficial for tailoring a more personalized treatment strategy combatting steroid resistance and frequent exacerbations in this group of patients.

Change in Allergy Practice during the COVID-19 Pandemic.

BACKGROUND: International guidelines in asthma and allergy has been updated for COVID-19 pandemic and pandemic has caused dramatic changes in allergy and immunology services. However, it is not known whether specialty-specific recommendations for COVID-19 are followed by allergists. OBJECTIVES: By conducting this study, we aimed to determine the attitudes and experiences of adult/pediatric allergists on allergy management during COVID-19. METHOD: We used a 20-question survey to elicit data from allergists (residents and pediatric and adult allergists registered to the Turkish National Society of Allergy and Clinical Immunology) across Turkey via e-mail. We analyzed the data statistically for frequency distributions and descriptive analysis. RESULTS: A total of 183 allergists participated in the survey. Telemedicine was used for management of asthma (73%), allergic rhinitis (53%), atopic dermatitis (51%), chronic urticaria/angioedema (59%), drug hypersensitivity (45%), food allergy (48%), venom allergy (30%), anaphylaxis (22%), and hereditary angioedema (28%). Thirty-one percent of the respondents discontinued subcutaneous immunotherapy (SCIT) during the COVID-19 pandemic. Thirty-four percent of the physicians reported interruption of systemic steroid use in asthma patients, and 25% of the respondents discontinued biological therapy. CONCLUSIONS: Allergists in Turkey have been using telemedicine at a high rate during the COVID-19 pandemic for asthma and rhinitis. The continuation rate of SCIT was low while the discontinuation rate of biologicals and systemic steroid use in asthma was high in Turkey.Our study results and learning from the experiences of other countries and specialties may help to optimize allergy practice and compatibility with international guidelines.

Greater magnitude of entheseal microdamage and repair in psoriatic arthritis compared with ankylosing spondylitis on ultrasound.

Objectives: AS and PsA share clinical and immunological features centred on enthesitis. However, a strong association between PsA and preceding injury has been recognized. The aim of this study was to test the hypothesis that the entheseal damage seen by US is commoner in PsA patients than in AS patients. Methods: Seventy-nine AS and 85 PsA patients had US scans of 1640 entheses to calculate entheseal inflammation (hypoechogenicity, thickening and Doppler) and damage scores (calcifications, enthesophytes and erosions). Regression modelling was done to evaluate the effect of diagnoses on outcomes, controlling for age, gender, BMI, clinical enthesitis, HLA-B27, and anti-TNF use. Results: Both inflammation and damage scores on US were correlated with BMI (r = 0.392; r = 0.320) and age (r = 0.308; r = 0.538) (P < 0.001), and men had higher inflammation scores than women [12.3 (7.5) vs 8.9 (7.3), P = 0.001]. In multivariate analysis, despite similar (anti-TNF-treated patients) or slightly less inflammation (anti-TNF-naïve patients) in the PsA group, they had 4.22 times more US damage than their counterparts with AS. The difference was even higher in the anti-TNF-naïve patients (5.6 times). Conclusion: On US assessment, PsA patients have greater entheseal insertion damage scores compared with AS, suggesting potential differences in tissue repair, immunobiology or response to injury at insertions.

Six-joint ultrasound in rheumatoid arthritis: a feasible approach for implementing ultrasound in remission.

OBJECTIVES: Subclinical disease activity in rheumatoid arthritis (RA) detected by imaging methods is predictive for flares and damage. Lack of time is the major limitation for not screening for subclinical disease in routine practice. We aimed to determine the most feasible protocol to screen patients with no clinical disease activity by ultrasound (US). METHODS: A hundred consecutive RA patients with no clinical activity according to the physician had an US scan for 38 joints. The prevalence of power Doppler (PD) signal in each joint was determined and different combinations of joints were assessed for their ability to capture this information. The most practical combination with a good sensitivity was tested in another group of 50 RA patients. RESULTS: Having any PD signal was not linked to the disease activity parameters whereas presence of PD of ≥2 was associated with higher DAS28CRP. Sixty patients had at least one joint with PD of grade ≥2 (60%). A combination of the wrists and 2nd-3rd MCP joints bilaterally (PD-6 joints) was able to detect 45/60 (75%) cases with PD signals and 45% of the whole patient population. The correlation between PD-38 and PD-6 joints was excellent (r=0.820, p<0.0001). PD-6 joints in the 2nd cohort was also able to detect 22/50 (44%) of the whole group. CONCLUSIONS: Subclinical disease activity could be detected in 60% of RA patients when 38 joints screened by US. Limiting the screening to wrists, 2nd-3rd MCPs bilaterally was acceptable as it detected 75% of cases with subclinical disease and increased the feasibility.

The Potential for Emerging Microbiome-Mediated Therapeutics in Asthma.

PURPOSE OF REVIEW: In terms of immune regulating functions, analysis of the microbiome has led the development of therapeutic strategies that may be applicable to asthma management. This review summarizes the current literature on the gut and lung microbiota in asthma pathogenesis with a focus on the roles of innate molecules and new microbiome-mediated therapeutics. RECENT FINDINGS: Recent clinical and basic studies to date have identified several possible therapeutics that can target innate immunity and the microbiota in asthma. Some of these drugs have shown beneficial effects in the treatment of certain asthma phenotypes and for protection against asthma during early life. Current clinical evidence does not support the use of these therapies for effective treatment of asthma. The integration of the data regarding microbiota with technologic advances, such as next generation sequencing and omics offers promise. Combining comprehensive bioinformatics, new molecules and approaches may shape future asthma treatment.

A case of uncontrolled severe asthma patient with coexisting carcinoid tumor presenting as pneumomediastinum.

INTRODUCTION: Patients with inadequately controlled or uncontrolled asthma are at a greater risk of attacks for asthma requiring emergency room visits or hospital admissions. There is a significant correlation between the severity of the disease and the severity of exacerbations. Patients with poorly controlled asthma are at a higher risk for complications. CASE STUDY: We present a 24-year-old aspirin-intolerant, uncontrolled asthma patient with the complication of pneumomediastinum. RESULTS: Severe symptoms persisted after the resolution of the pneumomediastinum despite intense anti-inflammatory and anti-obstructive therapy. A bronchoscopy revealed an endobronchial lesion and she was diagnosed with a carcinoid tumor. CONCLUSION: This case is an example of the importance of re-evaluating asthma patients who do not respond to standard medical treatment. Clinicians should be aware of the complications associated with asthma attacks such as pneumomediastinum and the possibility of a differential diagnosis that worsen asthma symptoms such as a carcinoid tumor.

Clinical and allergic sensitization characteristics of allergic rhinitis among the elderly population in Istanbul, Turkey.

Prevalence of allergic rhinitis (AR) in elderly population in Turkey is not known. Studies on the prevalence and features of allergy in older adults are needed to identify safe and effective diagnostic/therapeutic methods for elderly AR patients. We aimed to identify the clinical and allergic characteristics of sensitization to aeroallergens among individuals aged ≥60 years with allergic rhinitis admitted to an allergy outpatient clinic in Istanbul. Of 109 patients, 33.9 % were atopic. Sixty-five percent of subjects were sensitized to Dermatophagoides pteronyssinus, 17 % to a grass-pollen mixture, 8 % to Aspergillus fumigatus, and 8 % to Blattella germanica. There was no difference between mono- and polysensitized patients in terms of the duration of rhinitis and symptom severity. No significant difference was observed between the two groups according to age, sex, smoking status, AR onset (<40 or ≥40 years), or duration/severity of disease. There was no significant difference between the two groups in the prevalence of asthma and conjunctivitis, (p = 0.256). Atopic dermatitis/eczema was more prevalent in those with AR (p = 0.046). Clinical characteristics of AR in the elderly could be different from those in non-allergic patients, and the prevalence of allergy may be higher than expected.

Effect of smoking and indoor air pollution on the risk of tuberculosis: smoking, indoor air pollution and tuberculosis.

INTRODUCTION: Although epidemiological studies have reported an association between smoking and increases in tuberculosis, the relationship between indoor air pollution and risk of tuberculosis is not fully understood. A limited number of studies have suggested that smoking and indoor air pollution may play a role in the pathogenesis of tuberculosis. In this study, we investigated the effect of smoking and indoor air pollution on the risk of active tuberculosis. MATERIALS AND METHODS: It is prospectively recorded age matched case-control study. Three hundred sixty two active tuberculosis cases and 409 healthy controls were included to the study. All participants were interviewed face to face by using a questionnaire including smoking habit, quantity and duration of smoking, number of room/person in the house, monthly income of the family, indoor heating system, and environmental tobacco smoke. RESULTS: Patients who smoke had a five fold (95% CI: 3.2-7.5, p< 0.0001) higher odds of having active tuberculosis compared with patients who do not smoke. Similarly, patients using coal or wood for indoor heating had a 1.6 fold (95% CI: 1.179-2.305, p< 0.003) higher odds having tuberculosis. People who have less income (< 200 Euro/month) had 3.2 fold (95% CI: 2.113-5.106, p< 0.0001) higher odds of having tuberculosis compared with people having high income. There was a significant correlation between heavy smoking (≥ 20 packet/year, p< 0.0001) and age onset of smoking (< 16 years of age, p< 0.041). There was no significant association between environmental tobacco smoke and tuberculosis. CONCLUSION: Smoking and indoor air pollution may increase the risk of tuberculosis. There is a complex interaction between smoking, socioeconomic conditions, indoor air quality and tuberculosis. Our results suggest that effective indoor air quality control could help to prevent tuberculosis risk.

COVID-19, Severe Asthma and Omalizumab Therapy: A Case-Based Inquiry into Associations, Management, and the Possibility of a Better Outcome.

Recent developments in research have put forward claims on the protective effect of allergic diseases-especially allergic airway inflammation including allergic asthma-against the COVID-19 pandemic. This was first suggested by the underrepresentation of asthma patients in some cohorts and was later investigated by angiotensin-converting enzyme II (ACEII) receptor expression studies. Controversial data on this matter persists and continue to be a challenge for clinicians when it comes to managing allergic diseases during the pandemic. We present in this study a thorough review of related findings so far and our own experience with 2 severe asthma patients who presented with atypical symptoms. Interestingly, both patients were administered anti-IgE therapy prior to the initial positive polymerase chain reaction (PCR) results for COVID-19 and showed no symptoms of severe respiratory disease during the infection unlike what we know from other viral respiratory illnesses. Stemming from that, we wanted to combine the perspectives of allergists and infectious disease specialists to address certain concerns in the management of allergic diseases, such as biologicals, in the light of current guidelines. We have also pointed out certain gaps in clinical and molecular level research, such as the lack of phenotypicalsubgroup analysis among ill asthma patients and the lack of data concerning the molecular effects of biologicals on viral infection.

Microbiota - The Unseen Players in Adult Asthmatic Airways.

Modulation of human lung airway physiology by commensal microbiota has become one of the key mechanisms involved in the pathogenesis of adult asthma. Recent evidence suggests that the composition of respiratory microbiota plays a significant role in the manifestation of adult asthma; however, scientific evidence about the relationship between airway microbial diversity and phenotypes of adult asthma is limited. Further research is needed to understand the interactions between the airway microbiota and host immune response to develop microbiota-based strategies in management of adult asthma. This study reviews the advances in culture-independent methods for detection of airway microbiome, the current data about airway microbiota in healthy individuals and in adult patients with asthma with a focus on bacterial communities, and the future research directions in airway microbiome.

Bronchoscopy during the COVID-19 pandemic: A survey study.

BACKGROUND: In this study, we aimed to evaluate the attitudes and behaviors of physicians performing bronchoscopy during the COVID-19 outbreak. METHODS: Between March 2020 and May 2020, a total of 153 physicians were included in the study. An invitation letter for the participation in the study with a structured questionnaire of 18 questions were sent to the mail groups twice with five-day intervals. Participation in the study was allowed, until the third day after the second mail was sent. RESULTS: All participants completed the questionnaire. According to the results, 33% of the physicians did not perform bronchoscopy and the majority of the physicians performed very few procedures during the outbreak, although the participants mostly worked at the tertiary hospitals (mean: 7.2±9.3). A total of 20% of the physicians performed bronchoscopy in potential or proven COVID-19 patients. Almost all of the physicians who participated in the survey reported the use of personal protective equipment such as masks and goggles during the procedure. During the pandemic, 9.7% of the physicians who performed bronchoscopy to potential or proven COVID-19 patients and 4.1% of the participants who did not perform bronchoscopy to any potential or proven COVID-19 patients were found to be infected with the virus (p>0.05). CONCLUSION: Physicians who perform bronchoscopy during pandemic act in accordance with the recommendations of guidelines. Although there was no statistically significant difference between the SARS-CoV-2 transmission rates of the teams who performed and did not perform bronchoscopy in potential or proven COVID-19 patients in our study, the high rate of personal protective equipment utilization might have played a role in this result.

Immune profiling after minimally invasive lobectomy.

OBJECTIVES: Whether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer. METHODS: Blood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery. RESULTS: Minimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3+CD4+ and CD3+CD8+ CD16+CD56+ cell counts were significantly lower on postoperative day 1. CONCLUSION: There seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy.

Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019: A Multicenter, Prospective, Observational Clinical Trial.

Rationale: Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. Objectives: To determine the effect of OSA on clinical outcomes in patients with COVID-19. Methods: The current prospective observational study was conducted in three hospitals in Istanbul, Turkey from March 10 to June 22, 2020. The participants were categorized as high-risk or low-risk OSA according to the Berlin questionnaire that was administered in the out-patient clinic, in hospital, or shortly after discharge from hospital blinded to the clinical outcomes. A modified high-risk (mHR)-OSA score based on the snoring patterns (intensity and/or frequency), breathing pauses, and morning/daytime sleepiness, without taking obesity and hypertension into account, were used in the regression models. Results: The primary outcome was the clinical improvement defined as a decline of two categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death) on Days 7, 14, 21, and 28, respectively. Secondary outcomes included clinical worsening (an increase of 1 category), need for hospitalization, supplemental oxygen, and intensive care. In total, 320 eligible patients (median [interquartile range] age, 53.2 [41.3-63.0] yr; 45.9% female) were enrolled. In all, 121 (37.8%) were categorized as known (n = 3) or high-risk OSA (n = 118). According to the modified scoring, 70 (21.9%) had mHR-OSA. Among 242 patients requiring hospitalization, clinical improvement within 2 weeks occurred in 75.4% of the mHR-OSA group compared with 88.4% of the modified low-risk-OSA group (P = 0.014). In multivariate regression analyses, mHR-OSA (adjusted odds ratio [OR], 0.42; 95% confidence interval [CI], 0.19-0.92) and male sex (OR, 0.39; 95% CI, 0.17-0.86) predicted the delayed clinical improvement. In the entire study population (n = 320), including the nonhospitalized patients, mHR-OSA was associated with clinical worsening (adjusted hazard ratio, 1.55; 95% CI, 1.00-2.39) and with the need for supplemental oxygen (OR, 1.95; 95% CI, 1.06-3.59). Snoring patterns, especially louder snoring, significantly predicted delayed clinical improvement, worsening, need for hospitalization, supplemental oxygen, and intensive care. Conclusions: Adults with mHR-OSA in our COVID-19 cohort had poorer clinical outcomes than those with modified low-risk OSA independent of age, sex, and comorbidities. Clinical trial registered with www.clinicaltrials.gov (NCT04363333).

Anti-IL-5 Biologicals Targeting Severe Late Onset Eosinophilic Asthma.

Improved knowledge about the pathogenesis of asthma has facilitated the development of novel drugs and provided hope for patients with severe asthma. After the short- and long-term success of omalizumab in severe allergic phenotype, researchers have targeted patients with severe eosinophilic asthma who comprise up to 45% of adult severe asthma. Interleukin (IL)-5 and IL-5 receptor subunit α play crucial roles in the development, maturation, and operation of eosinophils. Currently, patients treated with anti-IL-5 biologicals depleting eosinophils experience the positive efficacy of these drugs, especially with regard to the reduction of exacerbation rate. The aim of this review was to shed light on severe eosinophilic asthma treatment with these new currently available agents selectively targeting IL-5 or its receptor, discussing their usage including pre-treatment concerns, such as selecting the target population and choosing the right agent among them, and subsequent assessment of relevant effect and safety issues.

The role of endobronchial ultrasonography elastography for predicting malignancy.

BACKGROUND: This study aims to investigate the role of endobronchial ultrasonography elastography in predicting malignancy. METHODS: Between January 2016 and December 2016, a total of 221 lymph nodes were biopsied using the endobronchial ultrasonography-guided transbronchial needle aspiration from 119 consecutive patients (69 males, 50 females; mean age 63.2±12.4 years; range, 16 to 86 years) were included. Lymph nodes were scored by elastography according to their colors in four categories before the procedure. The strain ratio was calculated based on the region of interest after three measurements. RESULTS: Of the patients, 93 were diagnosed with a malignancy through endobronchial ultrasonography-guided transbronchial needle aspiration biopsy. The mean lymph node score of benign versus malignant lesions was 2.2±1.0 and 3.2±1, respectively (p<0.001). There was a positive correlation between the lymph node scores and lymph node diameter, strain ratio, ≥3 of lymph node scoring, the sensitivity for malignancy was 79% and specificity was 60%. The mean strain ratio for malignant and benign lymph nodes was 22.2±30.1 and 5.2±1.7, respectively (p<0.001). With a cut-off value of ≥2.47 of strain ratio, the sensitivity for malignancy was 75% and specificity was 65%. The combined use of positron emission tomography and lymph node score or strain ratio yielded 80.4% and 61.2% sensitivity and 80% and 70.3% specificity for malignancy, respectively. CONCLUSION: Endobronchial ultrasonography elastography is useful in predicting malignancy of the lymph nodes. When combined with positron emission tomography, specificity and positive predictive value for malignancy increase.