Challenges and recommendations for the management of asthma in the Middle East and Africa.

Clinical presentation of asthma is variable, and its diagnosis can be a major challenge in routine health-care practice, especially in low-and-middle-income countries. The aim of asthma management is to achieve optimal asthma control and to reduce the risk of asthma exacerbations and mortality. In the Middle East and in Africa (MEA), several patient- and physician-related factors lead to misdiagnosis and suboptimal management of asthma. A panel of experts comprising of specialists as well as general health-care professionals met to identify challenges and provide recommendations for the management of asthma in MEA. The major challenges identified for diagnosis of asthma were lack of adequate knowledge about the disease, lack of specialized diagnostic facilities, limited access to spirometry, and social stigma associated with asthma. The prime challenges for management of asthma in MEA were identified as overreliance on short-acting ß-agonists (SABAs), underprescription of inhaled corticosteroids (ICS), nonadherence to prescribed medications, and inadequate insurance coverage for its treatment. The experts endorsed adapting the Global Initiative for Asthma guidelines at country and regional levels for effective management of asthma and to alleviate the overuse of SABAs as reliever medications. Stringent control over SABA use, discouraging over-the-counter availability of SABA, and using as-needed low-dose ICS and formoterol as rescue medications in mild cases were suggested to reduce the overreliance on SABAs. Encouraging SABA alone-free clinical practice in both outpatient and emergency department settings is also imperative. We present the recommendations for the management of asthma along with proposed regional adaptations of international guidelines for MEA.

A novel homozygous RTEL1 variant in a consanguineous Lebanese family: phenotypic heterogeneity and disease anticipation.

Phenotypic heterogeneity is often observed in patients with telomeropathies caused by pathogenic variants in telomere biology genes. However, the roles of recessive variants in these different phenotypes are not fully characterized. Our goal is to describe the biological roles of a novel homozygous RTEL1 variant identified in a consanguineous Lebanese family with unusual presentation of telomeropathies. A proband was screened for germline variants in telomere biology genes by whole exome sequencing. Leukocytes' telomere length was measured in the proband and eight relatives. We identified a novel homozygous p.E665K RTEL1 variant in the proband, his mother, and seven siblings that associated with telomere shortening and a broad spectrum of clinical manifestations, ranging from mild unspecific findings to severe phenotypes. Consanguinity in at least three family generations led to increased frequency of the homozygous p.E665K variant in the youngest generation and progressive telomere shortening. The increased frequency of the homozygous RTEL1 variant due to consanguinity in this Lebanese family allowed us to infer novel behaviors of recessive RTEL1 variants, as the expressivity and penetrance of this gene are very heterogenous between inter- and intra-generations. Progressive telomere shortening was associated with disease anticipation, first reported in recessive autosomal telomeropathies. Both genetic testing and telomere length measurement were critical for the clinical diagnosis of this family with telomere diseases marked by phenotypic heterogeneity.