CHARGE syndrome:a review of the immunological aspects

CHARGE syndrome is caused by a dominant variant in the CHD7 gene. Multiple organ systems can be affected because of haploinsufficiency of CHD7 during embryonic development. CHARGE syndrome shares many clinical features with the 22q11.2 deletion syndrome. Immunological abnormalities have been described, but are generally given little attention in studies on CHARGE syndrome. However, structured information on immunological abnormalities in CHARGE patients is necessary to develop optimal guidelines for diagnosis, treatment and follow-up in these patients. Here, we provide an overview of the current literature on immunological abnormalities in CHARGE syndrome. We also explore immunological abnormalities in comparable multiple congenital anomaly syndromes to identify common immunological phenotypes and genetic pathways that might regulate the immune system. Finally, we aim to identify gaps in our knowledge on the immunological aspects in CHARGE syndrome that need further study

Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry.

BACKGROUND: Investigation for the presence of asthma comorbidities is recommended by GINA as their presence can complicate asthma management. OBJECTIVE: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes. METHODS: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. Thirty comorbidities were identified and categorized a priori as either (1) potentially T2-related, (2) potentially oral corticosteroid (OCS)-related or (3) mimicking/aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex. RESULTS: Of 11,821 patients, 69%, 67%, and 55% had ≥1 potentially T2-related, potentially OCS-related, or mimicking/aggravating comorbidities, respectively; 57% had ≥3 comorbidities, and 33% had comorbidities in all three categories. Patients with allergic rhinitis (AR), nasal polyposis (NP), and chronic rhinosinusitis (CRS) experienced 1.12- (p=0.003), 1.16- (p<0.001) and 1.29-times (p<0.001) more exacerbations/year, respectively, than those without. Patients with NP and CRS were 40% and 46% more likely (p<0.001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with greater likelihood of LTOCS use (ORs: 1.23-2.77) and, except for dyslipidemia, with greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking/aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81) and all (except COPD) with increased likelihood of LTOCS use (ORs: 1.37-1.57). Greater number of comorbidities was associated with worse outcome. CONCLUSION: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes

Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

RATIONALE: Previous studies investigating comorbidity impact on biologic effectiveness have been relatively small, of short duration, and have not compared biologic classes. OBJECTIVES: To determine the association between T2-related comorbidities and biologic effectiveness in adults with severe asthma (SA). METHODS: This cohort study used International Severe Asthma Registry data (n=21 countries, 2017-2022) to quantify pre- to post-biologic change for four outcomes (annual asthma exacerbation rate, % predicted FEV1 (ppFEV1), asthma control, and long-term oral corticosteroid daily dose [LTOCS]) in patients with/without allergic rhinitis (AR), chronic rhinosinusitis +/- nasal polyps (CRS+/-NP), NP, or eczema/atopic dermatitis (AD). MAIN RESULTS: Of 1765 patients, 1257, 421, and 87 initiated anti-IL-5/5R, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- to post-biologic improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS+/-NP experienced 23% (95% CI 10-35%, p<0.001) fewer exacerbations/year and had 59% (95% CI: 26-102%, p<0.001) higher odds of better post-biologic control than those without CRS+/-NP. Similar estimates were noted for those with comorbid NP (22% less exacerbations and 56% higher odds of better post-biologic control). Patients with SA and CRS+/-NP had an additional ppFEV1 improvement of 3.2% (95% CI: 1.0-5.3; p=0.004), a trend that was also noted in those with comorbid NP. The presence of AR or AD were not associated with pre- to post-biologic effect for any outcome assessed. CONCLUSIONS: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS+/-NP or NP may be considered a predictor of biologic effectiveness in patients with severe asthma