Primary immunodeficiency and the microbiome.

PURPOSE OF REVIEW: The current understanding of the relationship of the microbiota to clinical manifestation in patients with primary immunodeficiency, specifically the inflammatory processes caused by or that result in microbial dysbiosis, and their potential therapeutic options in primary immunodeficiency diseases (PID), is the basis of this review. RECENT FINDINGS: PIDs are heterogeneous diseases with variable presentations, genetic backgrounds, complications, and severity. The immune-mediators may be extrinsic, such as therapeutic regimens that patients are on, including immunoglobin, biologics, antibiotics and diet, or intrinsic, like cytokines, microRNA and microbiome. The microbiome in PID, in particular, appears to play a crucial role in helping the host's immune system maintain hemostatic control in the intestine. Many of the clinical manifestations and complications of PID may be attributed to inflammatory and immune dysregulatory processes connected to the imbalances of the diet-microbiota-host-immunity axis, as shown by data pointing to the loss of microbial diversity, dysbiosis, in PID. SUMMARY: The gut microbiome is a promising area of study in PID. Although the connection of the microbiome to humoral immunodeficiency is evident, the possibility of utilizing the association of humoral and cellular immunodeficiency and the microbiome for therapeutic benefit is still under investigation.

Etiology and outcome of hemoptysis in Qatar, a high-resource country with a large expatriate population: A retrospective study.

Background: Hemoptysis is an alarming symptom in clinical practice. We reviewed ten years of experience with hemoptysis in a tertiary hospital in Qatar to identify hemoptysis etiologies, patient characteristics, and associated factors. Methods: Hemoptysis was defined based on severity as mild ( < 50 ml or streaks of blood), moderate (50-150 ml) and massive (>150 ml) in the 24 hours before admission. Hemodynamically unstable is considered when systolic BP  < 100 mmHg,tachycardia with HR>110/min, tachypnea with RR>22/min, or SpO2  < 92% on room air. Results: A total of 102 patients (41 females and 61 males) with 133 episodes of hemoptysis were identified in this study. Among the hemoptysis patients with co-morbidities, 19 patients had hypertension, 17 patients had cardiovascular disease, and 66 patients with other co-morbidities. COPD patients had a significant (p  <  0.02) association with hemoptysis. Chest X-ray was used in most patients and other modalities like CT scan and bronchoscopies were used less frequently. Pneumonia (12.8%), bronchiectasis (11.8%) and cardiovascular disorders (11.8%) are the primary causes of hemoptysis. Malignancy was less frequent (7.8%), and bronchogenic carcinoma was uncommon (2%). There were 24 (23.5 %) no identified causes of hemoptysis. The overall mortality was 9.8% in this study. Conclusions: Population demographics played a significant role in the severity of hemoptysis and prognosis. Most patients had benign etiologies, lower severity of hemoptysis and good prognosis. Differences in the etiology, initial severity, and prognosis of patients with hemoptysis were found significantly different when compared with those reported in previous studies.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

The first case report of complement component 7 deficiency in Qatar and a 10-year follow-up.

Introduction: Neisseria meningitidis is a significant cause of bacterial meningitis and septicemia worldwide. Recurrent Neisseria meningitidis is frequently associated with terminal complement protein deficiency, including Complement component 7. This report discusses the first case of C7 deficiency in Qatar. Case report: A 30-year-old Qatari man presented with a meningococcal infection, which was verified by a blood culture. He experienced two episodes of meningitis caused by an undetermined organism. His blood tests revealed low levels of CH50 and C7. His C7 gene testing revealed a homozygous mutation in exon 10 (c.1135G>C p.Gly379Arg), a mutation that has not been previously documented in Qatar. However, it has been observed in 1% of Moroccan-origin Israeli Jews who also exhibit C7 deficiency. Regular prophylactic quadrivalent vaccinations against types A, C, Y, and W-135 with azithromycin tabs were administered. Over the last 10 years of follow-up, he remained in good health, with no further meningitis episodes. Conclusion: To our knowledge, this is the first confirmed case of C7 deficiency reported in the Arabian Gulf countries. Such rare diseases should be a public health priority. Awareness among medical practitioners and the community should help with early detection of C7 deficiency and the prevention of its consequences.

Severe exercise-induced anaphylaxis in a hot and humid area successfully treated with omalizumab: a case report.

Exercise-induced anaphylaxis (EIA) is a rare disorder in which anaphylaxis occurs exclusively after physical activity. Here, we report a case of severe EIA where anaphylaxis was initially only induced by strenuous exercise. Suddenly the anaphylaxis got out of control to the degree that usual daily activities triggered it. Exposure to a hot and humid environment appeared to be a cofactor for the development of severe symptoms resistant to usual preventive measures. Treatment with omalizumab (anti-IgE) was initiated and resulted in marked improvement. We discuss unique aspects of this case in comparison to published information on the clinical features, triggering cofactors, diagnosis, and treatment of EIA.

Expert opinion on management of moderate-to-severe atopic dermatitis in Qatar.

Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous population, and regional clinical practices for treating AD warrant the development of guidelines in Qatar. Therefore, guidelines for the management of moderate-to-severe AD in Qatar have been developed and discussed. Experts, including dermatologists and immunologists, used the Delphi technique for developing guidelines. Consensus was defined as ≥75% agreement or disagreement. AD is highly prevalent in primary and tertiary dermatology centers. AD-associated foot eczema and psoriasiform eczema are more frequent in Qatar than in Europe or USA. SCORing Atopic Dermatitis Index quantifies disease severity and itch. Dermatology Life Quality Index assesses the quality of life. Atopic Dermatitis Control Tool assesses long-term disease control. Moderate-severe AD benefits from new topicals like Janus-kinase-inhibitors or PDE4-inhibitors combined with phototherapy. Currently approved systemic agents are dupilumab, baricitinib, abrocitinib, and upadacitinib. New anti-IL-13 and anti-IL-31 therapies will soon be available. Patient education, allergy testing, and comorbidity consideration are critical in the management of AD. The expert panel established a comprehensive and pragmatic approach to managing moderate-to-severe AD, thereby assisting clinical decision-making for healthcare professionals in Qatar.

Anaphylaxis after prick-to-prick skin test to seafood allergy: A rare adverse event.

Allergies to seafood are common all over the world. The prick-to-pricktest is used to diagnose allergic reactions. In this article, a femalepatient suffered an anaphylactic reaction 5 minutes following a Prick-to-Prick skin test. Therefore, it is important to stratify, recognize and treatthe anaphylactic reaction promptly.

Aerobiological monitoring in a desert type ecosystem: Two sampling stations of two cities (2017-2020) in Qatar.

BACKGROUND: The increasing number of aerobiological stations empower comparative studies to determine the relationship between pollen concentrations in different localities and the appropriate distance, which should be established between sampling stations. In Qatar, this is basically the first aerobiological study for a continuous monitoring interval. OBJECTIVES: The study aimed to assess the abundance and seasonality of the most prevalent pollen types, plus identify potential differences between two sites within the country. METHODS: Airborne pollen data were collected during 2017-2020 by using Hirst-type volumetric samplers in Doha capital city and Al Khor city in Qatar, placed 50 km apart. RESULTS: Higher total pollen indexes were recorded in the Al Khor station (2931 pollen * day/m3) compared to the Doha station (1618 pollen * day/m3). Comparing the pollen spectrum between the sampling stations revealed that ten pollen types were found in common. Amaranthaceae and Poaceae airborne pollen constituted 73.5% and 70.9% of the total amount of pollen detected at the samplers of Al Khor station and Doha station. In both sampling sites, a very pronounced seasonality was shown; August-October appeared as the period with the most intense incidence of atmospheric herbaceous pollen, with 71% and 51% of the annual total counts in Al Khor and Doha stations, respectively. August (Al Khor, 21%; Doha, 9%), September (Al Khor, 33%; Doha, 26%), October (Al Khor, 17%; Doha, 16%) were the months in which the herbs pollen concentrations were highest. Significant statistical differences between the two stations were observed in specific pollen types with local distribution in each trap's vicinity. CONCLUSIONS: Comparison of data obtained by the two samplers running at a distance of 50 Km indicated that potential inter-site differences could be attributed to the vegetation surrounding the city having a decisive influence on data collected.

The correlation between middle schoolchildren allergic symptoms and airborne particle season: A cross-sectional study.

ABSTRACT: Limited studies correlate allergic symptoms and associated outdoor biological particle exposure among schoolchildren globally.This study aimed to investigate the relationship between the seasonality of symptoms of allergic diseases among middle schoolchildren and the annual variation of airborne pollen and fungal spore in a hot and humid geographical region (Qatar).During November 2017 to January 2018, a self-reported study of middle schoolchildren living in the Doha capital city of Qatar was conducted, and data gathered were evaluated in relation to the collected monthly pollen and fungal spores. Participants' data were collected by conducting a survey based on a modified questionnaire adopted from the International Study of Asthma and Allergy in Childhood (ISAAC). The airborne pollen and fungal spore in Doha's atmosphere were extracted from the Doha aerobiology project (2017-2020).Among the 1000 distributed questionnaires, 100 were excluded due to significant missing data and 644 middle schoolchildren living in Doha city responded and were included in the final analysis. The symptoms of allergic rhinitis (AR) pattern among the responders with positive symptoms were strongly linked with the higher airborne fungal spore incidence during the month of November. Out of 331 students with positive symptoms, the prevalence of AR, lifetime wheeze, and eczema was 62.8%, 28.1%, and 26.6%, respectively. Asthma was significantly higher in Qatari (39.8%) compared to non-Qatari (26.7%) middle schoolchildren (P = .02).Outdoor aeroallergen may be a contributing factor in addition to other environmental and genetic predisposing factors for childhood atopic diseases in the prevalence rate of allergic symptoms among middle schoolchildren in the peninsula of Qatar.

A Retrospective Study of Non-Communicable Diseases amongst Blue-Collar Migrant Workers in Qatar.

Background: South Asian workers have a greater predisposition to non-communicable diseases (NCDs) that is exacerbated by migration and length of residence in host countries. Aims: To examine the association between length of residence in Qatar with diagnosis of NCDs in male blue-collar workers. Methods: A retrospective investigation of the electronic health records (EHRs) of 119,581 clinical visits by 58,342 patients was conducted. Data included age, nationality and confirmed ICD-10 diagnosis. Based on duration of residence, the population was divided into groups: ≤6 months, 6-12 months, 1-≤2 years, 2-≤5 years, 5-≤6 years, >6 years. It was assumed that the group that had been resident in Qatar for ≤6 months represented diseases that had been acquired in their countries of origin. Results: South Asian (90%) patients presented with NCDs at a younger (mean ± SD age of 34.8 ± 9.0 years) age. Diabetes and hypertension were higher in those who had just arrived (<6 months' group), compared to the other durations of residence groups. Conversely, acute respiratory infections, as well as dermatitis and eczema, all increased, perhaps a consequence of shared living/working facilities. Only patients with diabetes and hypertension visited the clinic multiple times, and the cost of medication for these NCDs was affordable, relative to earnings. Discussion/Conclusions: Blue-collar workers were predominantly South Asian, from lower socioeconomic classes, with early onset chronic NCDs. Notably, residence in Qatar gave them better access to affordable, significantly subsidized healthcare, leading to effective management of these chronic conditions.

Digital tools in allergy and respiratory care.

Patient care in the allergy and respiratory fields is advancing rapidly, offering the possibility of the inclusion of a variety of digital tools that aim to improve outcomes of care. Impaired access to several health care facilities during the COVID-19 pandemic has considerably increased the appetite and need for the inclusion of e-health tools amongst end-users. Consequently, a multitude of different e-health tools have been launched worldwide with various registration and access options, and with a wide range of offered benefits. From the perspective of both patients and healthcare providers (HCPs), as well as from a legal and device-related perspective, several features are important for the acceptance, effectiveness,and long-term use of e-health tools. Patients and physicians have different needs and expectations of how digital tools might be of help in the care pathway. There is a need for standardization by defining quality assurance criteria. Therefore, the Upper Airway Diseases Committee of the World Allergy Organization (WAO) has taken the initiative to define and propose criteria for quality, appeal, and applicability of e-health tools in the allergy and respiratory care fields from a patient, clinician, and academic perspective with the ultimate aim to improve patient health and outcomes of care.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

In vitro Interleukin-7 treatment partially rescues MAIT cell dysfunction caused by SARS-CoV-2 infection.

MAIT cells have been shown to be activated upon several viral infections in a TCR-independent manner by responding to inflammatory cytokines secreted by antigen-presenting cells. Recently, a few studies have shown a similar activation of MAIT cells in response to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. In this study, we investigate the effect of SARS-CoV-2 infection on the frequency and phenotype of MAIT cells by flow cytometry, and we test in vitro stimulation conditions on the capacity to enhance or rescue the antiviral function of MAIT cells from patients with coronavirus disease 2019 (COVID-19). Our study, in agreement with recently published studies, confirmed the decline in MAIT cell frequency of hospitalized donors in comparison to healthy donors. MAIT cells of COVID-19 patients also had lower expression levels of TNF-alpha, perforin and granzyme B upon stimulation with IL-12 + IL-18. 24 h' incubation with IL-7 successfully restored perforin expression levels in COVID-19 patients. Combined, our findings support the growing evidence that SARS-CoV-2 is dysregulating MAIT cells and that IL-7 treatment might improve their function, rendering them more effective in protecting the body against the virus.

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways.

BACKGROUND: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. OUTCOMES: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

A Novel STAT3 Mutation in a Qatari Patient With Hyper-IgE Syndrome.

Autosomal dominant hyper-IgE syndrome caused by mutations in the transcription factor STAT3 (AD-HIES) is characterized by a collection of immunologic and non-immune features including eczema, recurrent infections, elevated IgE levels, and connective tissue anomalies. We report the case of a Qatari child with a history of recurrent staphylococcal skin infections since infancy, who was found to have a novel, de novo mutation in STAT3 (c.1934T>A, p.L645Q). The absence of mucocutaneous candidiasis and undetectable IgE levels until the age of 7 years prolonged the time to molecular confirmation of the cause for the patient's immune deficiency. STAT3 p.L645Q was found to have decreased transcriptional capacity. The patient also had low levels of Th17 cells and STAT3 phosphorylation was impaired in patient-derived cells. Nearly 100 unique mutations in STAT3 have been reported in association with AD-HIES.