Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis.

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in cystic fibrosis (CF) patients homozygous or heterozygous for F508del mutation. The aim of the study was to evaluate the response to ELX/TEZ/IVA treatment both clinically and morphologically in terms of bronchiectasis, bronchial wall thickening, mucus plugging, abscess and consolidations. METHODS: We retrospectively collected data from CF patients followed at Parma CF Centre (Italy) treated by ELX/TEZ/IVA between March and November 2021. Post-treatment changes in respiratory function, quality of life, sweat chloride concentration, body mass index, pulmonary exacerbations and lung structure by chest magnetic resonance imaging (MRI) were assessed. T2-and T1-weighted sequences were acquired with a 20 min-long scanning protocol on a 1.5T MRI scanner (Philips Ingenia) without administration of intravenous contrast media. RESULTS: 19 patients (32.5 ± 10.2 years) were included in the study. After 6 months of treatment with ELX/TEZ/IVA, MRI showed significant improvements in the morphological score (p < 0.001), with a reduction in bronchial wall thickening (p < 0.001) and mucus plugging (p 0.01). Respiratory function showed significant improvement in predicted FEV1% (58.5 ± 17.5 vs 71.4 ± 20.1, p < 0.001), FVC% (79.0 ± 11.1 vs 88.3 ± 14.4, p < 0.001), FEV1/FVC (0.61 ± 0.16 vs 0.67 ± 0.15, <0.001) and LCI2.5% (17.8 ± 4.3 vs 15.8 ± 4.1 p < 0.005). Significant improvement was found in body mass index (20.6 ± 2.7 vs 21.9 ± 2.4, p < 0.001), pulmonary exacerbations (2.3 ± 1.3 vs 1.4 ± 1.3 p 0.018) and sweat chloride concentration (96.5 ± 36.6 vs 41.1 ± 16.9, p < 0.001). CONCLUSIONS: Our study confirms the efficacy of ELX/TEZ/IVA in CF patients not only from a clinical point of view but also in terms of morphological changes of the lungs.

Long COVID in Children and Adolescents.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise concern: multisystem inflammatory syndrome in children (MIS-C) and long COVID. While the understanding and the experience regarding the acute phase of SARS-CoV-2 infection have remarkably increased over time, scientific and clinical research is still exploring the long-term effects of COVID-19. In children, data on long COVID are scant. Reports are conflicting regarding its prevalence, duration and impact on daily life. This narrative review explored the latest literature regarding long COVID-19 in the pediatric population. We showed that long COVID in children might be a relevant clinical problem. In most cases, the prognosis is good, but some children may develop long-term symptoms with a significant impact on their daily life. The paucity of studies on long COVID, including a control group of children not infected by SARS-CoV-2, prevents us from drawing firm conclusions. Whether the neuropsychiatric symptoms widely observed in children and adolescents with long COVID are the consequence of SARS-CoV-2 infection or are due to the tremendous stress resulting from the restrictions and the pandemics is still not clear. In both cases, psychological support can play a fundamental role in managing COVID pandemics in children. More knowledge is needed to share a standardized definition of the syndrome and improve its management and treatment.

Clinical Impact of Aspergillus fumigatus in Children with Cystic Fibrosis.

Background. The clinical relevance of Aspergillus fumigatus (Af) in cystic fibrosis (CF) is controversial. The aims of the study were to assess the prevalence of Af disease in our cohort of CF patients and evaluate whether allergic bronchopulmonary aspergillosis (ABPA) and sensitization to Af affected lung function, body mass index (BMI) and exacerbations. Methods. Clinical data and lung function of CF patients aged 6−18 years followed at the CF Centre of Parma (Italy) were recorded. Patients were classified as: patients with no signs of Af, patients sensitized or colonized by Af, patients with ABPA or patients with Aspergillus bronchitis (Ab). Results. Of 38 CF patients (14.2 years (6.2−18.8) M 23), 8 (21%) showed Af sensitization, 7 (18.4%) showed ABPA, 1 (2.6%) showed Af colonization and 1 (2.6%) showed Ab. Compared to non-ABPA, patients with ABPA had lower BMI (15.9 ± 1.6 vs. 19.7 ± 3.4, p < 0.005), lower lung function (FEV1 61.5 ± 25.9% vs. 92.3 ± 19.3%, p < 0.001) and more exacerbations/year (4.43 ± 2.44 vs. 1.74 ± 2.33, p < 0.005). Patients with Af sensitization showed more exacerbations/year than non-Af patients (3.5 ± 3.2 vs. 0.9 ± 1.2, p < 0.005). ABPA and sensitized patients had more abnormalities on chest CT scans. Conclusion. This study showed the relevant clinical impact of ABPA and Af sensitization in terms of exacerbations and lung structural damage.

Management of Preschool Wheezing: Guideline from the Emilia-Romagna Asthma (ERA) Study Group.

Preschool wheezing should be considered an umbrella term for distinctive diseases with different observable and measurable phenotypes. Despite many efforts, there is a large gap in knowledge regarding management of preschool wheezing. In order to fill this lack of knowledge, the aim of these guidelines was to define management of wheezing disorders in preschool children (aged up to 5 years). A multidisciplinary panel of experts of the Emilia-Romagna Region, Italy, addressed twelve different key questions regarding the management of preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes) and systematic reviews have been conducted on PubMed to answer these specific questions, with the aim of formulating recommendations. The GRADE approach has been used for each selected paper, to assess the quality of the evidence and the degree of recommendations. These guidelines represent, in our opinion, the most complete and up-to-date collection of recommendations on preschool wheezing to guide pediatricians in the management of their patients, standardizing approaches. Undoubtedly, more research is needed to find objective biomarkers and understand underlying mechanisms to assess phenotype and endotype and to personalize targeted treatment.