Pediatric Pulmonology最新文献

Background: Immune-based therapy targeting immunoglobulin E (IgE), anti-IgE treatment, has emerged as an adjunct treatment for children with severe allergic asthma. After start of anti-IgE treatment, an effect of the treatment cannot be monitored by Total-IgE, because current methods measure both bound and free IgE molecules. Basophil activation test may be very useful for monitoring anti-IgE treatment efficacy. The objective of this paper is to evaluate if basophil activation test is applicable in regulating the anti-IgE treatment.

Methods: A case series of 20 children with IgE-mediated severe allergic asthma were treated according to guidelines with anti-IgE (Omalizumab). Blood samples were drawn for total IgE, specific IgE, number of IgE receptors (FcεRI) and basophil sensitivity were measured at baseline before anti-IgE treatment and 4 months after initiation of anti-IgE treatment.

Results: A total of 19 out of 20 children had statistically significant and clinically relevant effects of anti-IgE treatment on symptom score, lung function and medication. All 20 children had a significant reduction in basophil allergen sensitivity and the number of IgE receptors (FcεRI) on blood basophils. Anti-IgE treatment was found to be well controlled by measuring basophil allergen sensitivity and FceRI density on blood basophils.

Conclusion: This cohort study demonstrates a promising method, measuring basophil allergen sensitivity and in particular blood basophil FceRI density, concerning the monitoring of anti-IgE treatment in different clinical situations. There are no randomized controlled trials evaluating this method in clinical settings.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a significant impact on tuberculosis (TB) control globally, with the number of new TB diagnoses decreasing. Coinfection with some viruses, especially measles, could aggravate TB in children. This is presumably a result of depressed cellular immunity. Reports on children with TB and SARS-CoV-2 coinfection are limited.

Methods: A retrospective analysis of children up to 13 years old admitted to Tygerberg Hospital, Cape Town, South Africa, from March 2020 to December 2022 with suspected TB-induced airway compression requiring bronchoscopy. Children were included if they presented with severe intrathoracic airway obstruction and/or radiographic evidence of complicated TB. The patients were divided into two groups based on SARS-CoV-2 respiratory polymerase chain reaction results. Demographics, TB exposure, microbiology, SARS-CoV-2 laboratory data, imaging, inflammatory cytokine levels, and bronchoscopy data were collected. Statistical analyses compared SARS-CoV-2 positive and negative groups.

Results: Of the 50 children undergoing bronchoscopy for TB airway obstruction, 7 (14%) were SARS-CoV-2 positive. Cough was more prevalent in the SARS-CoV-2 positive group (p = 0.04). There was no difference in TB culture yield between groups. However, SARS-CoV-2 positive children showed slower radiological improvement at 1 month (p = 0.01), pleural effusions (p < 0.001), and a higher need for endoscopic enucleation (p < 0.001). FDG PET/CT scans indicated an ongoing inflammation in the SARS-CoV-2 positive group.

Conclusions: Coinfection with SARS-CoV-2 in children with TB airway obstruction appears to complicate the disease course, necessitating more medical interventions and demonstrating a longer duration of the TB inflammatory process. Further research is needed to understand the impact of viral infections on TB progression and outcomes in pediatric patients.

Rationale: Cardiopulmonary dysfunction is a major contributor to mortality among persons with sickle cell disease (pwSCD). Despite this, little is known regarding environmental drivers of lung function decline.

Objective: We hypothesized that environmental and socioeconomic variables have a significant effect on lung function in pwSCD that can be detected by spirometry.

Methods: We retrospectively analyzed all spirometry results from pwSCD followed in the Pediatric Pulmonology clinic at the Children's Hospital of Philadelphia since 1 January 2016.

Results: The study included 349 spirometry tests from 128 patients, primarily "Black or African American" (88%) and male (61%). More frequent exposure to PM2.5 above 25 μg/m³ was associated with higher odds of obstruction. Specifically, when compared to incidence of exposure to PM2.5 above 25 μg/m³ <25th percentile, both pwSCD exposed to 25th-75th percentile and pwSCD >75th percentile had higher odds of obstruction on spirometry (25th-75th: odds ratio [OR]: 9.6, p = .017; >75th: OR: 31.85, p = .002) despite correction for potential confounders. Similarly, median household income below the mean was associated with higher odds of restriction (OR: 4.37; p = .009).

Conclusions: We report higher odds of obstruction in pwSCD frequently exposed to PM2.5 concentrations above 25 μg/m³ and higher odds of restriction in pwSCD with lower household income. Our findings link spirometry patterns to modifiable risk factors indicating that there may opportunities for early intervention in pwSCD that have been referred to a pulmonology clinic. Further research is needed to assess if these findings can be generalized to the wider population of pwSCD.

Objectives: To compare the efficacy and safety of different vasodilators in the treatment of persistent pulmonary hypertension of the newborn (PPHN) by a Bayesian network meta-analysis.

Methods: We searched databases (Cochrane, PubMed, Embase, and Web of Science) from January, 1990 up to December, 2023. Randomized controlled trials on the use of vasodilators in the treatment of PPHN. We extracted details of population, intervention, and outcome indicators. R and STATA software were used for data analysis. Sixteen articles were included, encompassing 776 neonates with PPHN. Among them, 12 articles were included in the quantitative analysis. The vasodilators included Sildenafil, Bosentan, Milrinone, Magnesium, Adenosine, and Tadalafil.

Results: The Bayesian network meta-analysis results suggested that compared to placebo, Milrinone [OR = 0.125, 95% CI (0.0261, 0.562)], Sildenafil [OR = 0.144, 95% CI (0.0428, 0.420)], and Sildenafil_Milrinone [OR = 0.0575, 95% CI (0.00736, 0.364)] reduced the mortality, but the difference among the three was not significant. There was also no significant difference in the incidence of hypotension, the duration of mechanical ventilation, and the use of extracorporeal membrane oxygenation among the vasodilators. Compared to Bosentan, Adenosine was more effective in reducing the oxygenation index [MD = -12.78, 95% CI (-25.56, -0.03)], and Magnesium was less effective in reducing the oxygenation index than Sildenafil [MD = 5.19, 95% CI (1.23, 9.2)].

Conclusions: Milrinone, Sildenafil, and Sildenafil_Milrinone reduced the mortality of neonates with PPHN. More clinical trials are needed to verify the efficacy and safety of vasodilators in the treatment of PPHN.

Introduction: The triple combination of elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved the outcome of people with Cystic Fibrosis (pwCF) with at least one F508del mutation. However, carriers of rare cystic fibrosis transmembrane conductance regulator (CFTR) variants are not candidates for this innovative treatment.

Methods: In this observational study, we report the results of the compassionate use of ETI in 10 pwCF carriers of rare mutations after 2 months of treatment. Rectal organoids and short-term cultures of nasal epithelium obtained from rectal suction biopsies and nasal brushing were obtained from four subjects.

Results: After 2 months of ETI, all patients (4 males, mean age 30.1 ± 13.3 years) showed a significant increase of FEV₁% predicted values [+8.0 (3.5-12.7) %, p < 0.010], body mass index [+0.85 (0-1.22) kg/m², p < 0.020] and cystic fibrosis questionnaire-revised [+19.5 (6.3-29.2) points, p < 0.009]. A significant decrease of sweat chloride concentration [-11.2 (-1.7 to -34.0) mmol/L, p < 0.020] and exacerbations [-1.5 (-2 to -1), p < 0.008] was also recorded. Overall, 7 out of 10 participants were considered full responders. All patients reported cough disappearance (n = 3) or reduction (n = 7). Long-term oxygen was discontinued in two out of three patients and one also stopped noninvasive ventilation and was removed from the lung transplantation waiting list.

Conclusions: Despite the limited number of cases, our results support the use of CFTR modulators in patients with rare CFTR variants that are not currently approved for ETI in Europe.

Background: Cystic Fibrosis (CF) is associated with compromised nutrition status, which is responsible for morbidity and mortality along with lung function decline. This study was designed to examine changes in anthropometric markers and body composition parameters by bioelectrical impedance analysis after CFTR modulator (CFTRm) treatment.

Methods: We compared anthropometric parameters and body composition before and after 6 and 12 months of CFTRm treatment. Results are stratified into subgroups according to the modulator used with dual therapy with lumacaftor + ivacaftor or tezacaftor + ivacaftor (LUMA/TEZ + IVA) or triple therapy with elexacaftor + tezacaftor + ivacaftor (ELE + TEZ + IVA). Body composition data are available in patients treated with ELE + TEZ + IVA.

Results: Two hundred and thirty-four children (55.1% male) were recruited. The median age was 13.6 years (inter-quartile range [IQR] 10.7-16.1). We can observe a statistically significant increase in the weight Z score and BMI Z score after CFTRm. In terms of changes in body composition, we observe a significant increase in fat mass (FM) expressed both in kilograms and as a percentage at 6 months (p < .05; Wilcoxon-test), with no such differences found at 12 months. We also observe a statistically significant increase in fat-free-mass (FFM), expressed in kilograms at 6 and 12 months (p < .05; Wilcoxon-test).

Conclusion: Weight status improved and changes in body composition occurred in children after CFTRm therapy, including an increase of fat mass. Further studies are needed to confirm these changes in body composition and their impact on disease progression.