Introduction This study investigates drivers of childhood pulmonary tuberculosis (PTB) using a childhood ecosystem approach in South Africa. An ecosystem approach towards identifying risk factors for PTB may identify new directions for intervention. Methods Data were collected as part of a prospective cohort study of children presenting at a primary care facility or tertiary hospital with suspected TB. Characterization of the childhood ecosystem included proximal, medial and distal determinants. Proximal determinants included child characteristics that could impact PTB outcomes. Medial determinants included relational factors such as caregiver health that might impact interactions with the child. Distal determinants included macro-level determinants of disease such as socioeconomic status and food insecurity. Children started on TB treatment were followed for up to 6 months. Multivariate regression models tested independent associations between factors associated with PTB in children. Results Of 1,738 children enrolled in the study, 242 (20%) of children had confirmed PTB, 756 (63%) were started on TB treatment, and 444 (37%) had respiratory conditions other than TB. In univariate analyses, childhood malnutrition and caregiver smoking were associated with treated or confirmed PTB. In multivariate analyses, proximal factors such as male gender and hospitalization and low socio-economic status as a distal factor were associated with PTB. Conclusions Interventions may need to target subgroups of children and families at elevated risk for PTB. Screening for risk factors such caregiver health may guide targeting, and provision of social protection programs to bolster economic security may be important interventions for attenuating childhood exposure to risk factors.
Background Prenatal origins of wheezing are not fully understood. This study develops a model of mechanisms linking perinatal stress exposure to wheeze phenotypes in children. Methods Data were obtained from 1,849 mother-child dyads participating in ELSPAC-CZ birth cohort. Wheeze phenotypes assessed between birth and age seven years included “never wheeze”, “early-onset transient (EOT) wheeze,” “early-onset persistent (EOP) wheeze,” and “late-onset (LO) wheeze.” Prenatal and postnatal maternal stress exposures were assessed in mid-pregnancy and six months post-delivery, respectively, using an inventory of 42 life events. Results In adjusted models, children in the highest tercile (high) vs. lowest tercile (low) of prenatal life events had a 44% higher risk of EOT wheeze (relative risk ratio [RRR]=1.44, 95% confidence interval [CI]=1.06-1.95, p=0.02) and 69% higher risk of LO wheeze (RRR=1.69, 95% CI=1.13-2.52, p=0.01). High vs. low exposure to postnatal life events predicted a 74% increase in the risk of EOT wheeze (RRR=1.74, 95% CI=1.27-2.38, p<0.001) and 101% increase for EOP wheeze (RRR=2.01, 95% CI=1.23-3.26, p=0.005). Postnatal life events partially mediated between prenatal life events and any wheeze (high vs. low life events: indirect effect OR=1.13, 95% CI=1.06-1.21, p<0.001). Lower respiratory tract infections and secondary smoke partially mediated between postnatal life events and any wheeze (indirect effects OR=1.06, 95% CI=1.02-1.09, p=0.002 and OR=1.02, 95% CI 1.001-1.05, p=0.035, respectively). Conclusions Exposures to prenatal and postnatal life events are risk factors for development of wheezing. Prenatal stress contributes to wheeze directly and also through postnatal life events and respiratory infections.
Abstract Background and Objectives: Better phenotyping of the heterogenous bronchiolitis syndrome may lead to targeted future interventions. This study aims to identify severe bronchiolitis profiles among hospitalised Australian Indigenous infants, a population at high-risk of bronchiectasis, using Latent Class Analysis (LCA). Methods: We included prospectively collected clinical, viral and nasopharyngeal bacteria data from 164 Indigenous infants hospitalised with bronchiolitis. We undertook multiple correspondence analysis (MCA) followed by LCA. The best-fitting model for LCA was based on adjusted Bayesian information criteria and entropy R2. Results: We identified five clinical profiles. Profile-A’s (23.8% of cohort) phenotype was previous preterm (90.7%), low birth-weight (89.2%) and weight-for-length z-score <-1 (82.7% from combining those with z-score between -1 and -2 and those in the z-score of <-2 group) previous respiratory hospitalisation (39.6%) and bronchiectasis on chest high-resolution computed tomography scan (35.4%). Profile-B (25.3%) was characterised by oxygen requirement (100%) and marked accessory muscle use (45.5%). Infants in profile-C (7.0%) had the most severe disease, with oxygen requirement and bronchiectasis in 100%, moderate accessory muscle use (85% vs 0-51.4%) and bacteria detected (93.1% vs 56.7-72.0%). Profile-D (11.6%) was dominated by rhinovirus (49.4%), mild accessory muscle use (73.8%) and weight-for-length z-score <-2 (36.0%). Profile-E (32.2%) included bronchiectasis (13.8%), RSV (44.0%), rhinovirus (26.3%) and any bacteria (72%). Conclusions: Using LCA in Indigenous infants with severe bronchiolitis, we identified 5 clinical profiles with one distinct profile for bronchiectasis. LCA can characterise distinct phenotypes for severe bronchiolitis and infants at risk for future bronchiectasis, which may inform future targeted interventions.
Introduction Childhood cancer survivors (CSs) might face an increased lifelong risk of lung function impairment. The Lung Clearance Index (LCI) has been described as being more sensitive than spirometry in the early stages of some lung diseases. The aim of this study was to evaluate this index in a cohort of patients with a history of childhood cancer for the first time. Materials and Methods We evaluated 57 off-treatment CSs aged 0–18 years old and 50 healthy controls (HCs). We used the multiple breath washout (MBW) method to study LCI and spirometry. Results CSs did not show any differences from the controls in ventilation homogeneity (LCI 6.78 ± 1.35 vs. 6.32 ± 0.44, P: ns) or lung function (FEV1 99.9 ± 11.3% vs. 103.0 ± 5.9% of predicted, P: ns; FVC 98.2 ± 10.3% vs. 101.1 ± 3.3% of predicted). LCI significantly correlated with the number of years since the last chemotherapy (r = 0.35, P < 0.05). Conclusions Our study describes the trend of LCI in a cohort of CSs and compares it with the results obtained from healthy controls. The results show that patients maintain both good values of respiratory function and good homogeneity of ventilation during childhood. Moreover, the LCI identifies the tendency toward pulmonary fibrosis, which is typical of adult CSs, at an earlier time than spirometry.
Background: High frequency (HF) oscillatory ventilation has been shown to improve CO2 clearance in premature infants. In a previous in vitro lung model with normal lung mechanics we demonstrated significantly improved CO2 washout by HF oscillation of bubble CPAP (BCPAP). Objective: To examine CO2 clearance in a premature infant lung model with abnormal lung mechanics via measurement of end-tidal CO2 levels (EtCO2) while connected to HF oscillated BCPAP. Design/Methods: A 40mL premature infant lung model with either: normal lung mechanics (NLM): compliance 1.0 mL/cmH2O, airway resistance 56 cmH2O/(L/s); or abnormal lung mechanics (ALM): compliance 0.5 mL/cmH2O, airway resistance 136 cmH2O/(L/s), was connected to BCPAP with HF oscillation at either 4,6,8,10 or 12 Hz. EtCO2 was measured at BCPAPs of 4,6 and 8 cmH2O and respiratory rates (RR) of 40,60 and 80 breaths/min and 6mL tidal volume. Results: HF oscillation decreased EtCO2 levels at all BCPAPs, RRs, and oscillation frequencies for both lung models. Overall mean±SD EtCO2 levels decreased (p<0.001) from non-oscillated baseline by 19.3±10.2% for NLM vs. 14.1±8.8% for ALM. CO2 clearance improved for both lung models (p<0.001) as a function of oscillation frequency and RR with greatest effectiveness at 40-60 breaths/min and HF at 8-12 Hz. Conclusions: In this in-vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO2 clearance as compared to non-oscillated BCPAP for both NLM and ALM. The significant improvement in CO2 clearance in an abnormal lung environment is an important step towards clinical testing of this novel respiratory support modality.
Introduction: The prognosis of cystic fibrosis (CF) has dramatically changed over the past decade in France, mostly due to global improvements in specific care. Currently, the majority of French CF patients are adults, meaning they went through a transition process from a pediatric CF center to an adult CF center. To determine the impact of that transfer on clinical evolution, we report the transition procedure of our CF center in Lyon. Materials and Methods: From January 2006 to December 2016, 117 CF patients went through a standardized transition process from the pediatric to the adult CF center of Lyon. We compared the clinical evolution of the patients over 3 periods starting the year before transfer and ending the next year after transfer. Clinical data taken into account were FEV1%, BMI, pulmonary colonization, number of antibiotic courses, and number of days of hospitalization per year and outpatient visits per year. Results: No significant differences were observed between respiratory and nutritional status, pulmonary colonization, number of antibiotic courses, and numbers of hospitalizations and visits when comparing the 3 periods of observation (the year before, the year after and the next year after transfer) around transition. Conclusion: The standardized procedure of transition in Lyon is associated with the maintenance of a stable clinical status of our CF patients.
Cystic fibrosis is an autosomal recessive disease caused by CFTR gene mutations. Despite having the same mutation, CF patients may demonstrate clinical variability in severity and prognosis of the disease. In this study, we aimed to determine differentially expressed genes and associated molecular pathways between mild and severe siblings with same genotype. We performed targeted real-time PCR based transcriptomic analysis of nasal epithelial cells obtained from two families with two siblings with Class II mutations (F508del/F508del) and (F508del/G85E), one family with three siblings with Class IV mutation (I1234V/I1234V). In severe siblings with Class II mutations, TNFRSF11A, KCNE1, STX1A, SLC9A3R2 were found to be up regulated. CXCL1, CFTR, CXCL2 were found to be down regulated. Inflammation-immune response related signaling pathways such as IL-17, NF-kappa B, TNF, NOD-like receptor signaling were identified. In the severe sibling with Class IV mutation; inflammation and immune response-related pathways were discovered. Also, AGE-RAGE and TLR signaling were found to be specific to Class IV group. Comparison of CF patients to non-CF control; showed that ICAM1 was up regulated whereas EZR, TNFRSF1A, HSPA1A were down regulated in patients. In addition, a significant positive correlation was determined between differentially expressed genes in AGE-RAGE, cytokine-cytokine receptor interaction, insulin resistance and hepatic involvement in CF patients. As a result of this study, differentially expressed genes and associated pathways responsible for clinical severity among affected siblings carrying the same mutation were identified. The results will provide an opportunity for the development of novel target molecules for treatment of disease.
Background: The novel coronavirus disease (Covid-19) can progress with mild to moderate or self-limiting clinical findings in children. The aim of this study was to investigate the disease features of Covid-19 in Turkish children. Methods: Children diagnosed by the method of RT-PCR for Covid-19 at the Dicle University Department of Pediatric, between April and June 2020, were evaluated. Hospital records were investigated retrospectively. Results: One hundred and five patients children with the mean age of 108.64±65.61 were enrolled in this study. The most common cause of transmission in pediatric patients was contacting with a family member diagnosed with COVID-19 (n=91, 86.7%).The most common admission complaints were dry cough (n=17, 16.2%), fever (n=16, 15.2%), lassitude and fatigue (n=14, 13.3%) respectively. More than 95 % of all children with Covid-19 had asymptomatic, mild, or moderate cases. CRP was identified only independent factor associated with long duration of hospitalization. Conclusion: The results of this study show preliminary results of a study investigating the effect of Covid-19 on Turkish children. A clear understanding of the local epidemiology of corona virus infections and identification of risk factors is critical for the successful implementation of the prevention and control program.
Background: Multiple breath washout (MBW) is increasingly used in the clinical assessment of patients with cystic fibrosis (CF). Guidelines for MBW quality control (QC) were developed primarily for retrospective assessment and central overreading. We assessed whether real-time QC of MBW data during the measurement improves test acceptability in the clinical setting. Methods: We implemented standardized real-time QC and reporting of MBW data at the time of the measurement in the clinical pediatric lung function laboratory in Bern, Switzerland in children with CF aged 4-18 years. We assessed MBW test acceptability before (31 tests; 89 trials) and after (32 tests; 97 trials) implementation of real-time QC and compared agreement between reviewers. Further, we assessed the implementation of real-time QC at a secondary center in Zurich, Switzerland. Results: Before implementation of real-time QC in Bern, only 68% of clinical MBW tests were deemed acceptable following retrospective QC by an experienced reviewer. After implementation of real-time QC, MBW test acceptability improved to 84% in Bern. In Zurich, after implementation of real-time QC, test acceptability improved from 50% to 90%. Further, the agreement between MBW operators and an experienced reviewer for test acceptability was 97% in Bern and 100% in Zurich. Conclusion: Real-time QC of MBW data at the time of measurement is feasible in the clinical setting and results in improved test acceptability.
Nitric oxide (NO) is a comprehensive regulator of vascular and airway tone. Endogenous NO produced by nitric oxide synthases regulates multiple signaling cascades, including activation of soluble guanylate cyclase to generate cGMP, relaxing smooth muscle cells. Inhaled NO is an established therapy for pulmonary hypertension, especially in neonates, and has been recently proposed for treatment of hypoxic respiratory failure and acute respiratory distress syndrome due to COVID-19. In this review, we summarize the effects of endogenous and exogenous NO on protein S-nitrosylation, which is the selective and reversible covalent attachment of a nitrogen monoxide group to the thiol side chain of cysteine. This post-translational modification targets specific cysteines based on the acid/base sequence of surrounding residues, with significant impacts on protein interactions and function. S-nitrosothiol (SNO) formation is tightly compartmentalized and enzymatically controlled, but also propagated by non-enzymatic transnitrosylation of downstream protein targets. Redox-based nitrosylation and denitrosylation pathways dynamically regulate the equilibrium of SNO-proteins. We review the physiological roles of SNO proteins, including nitrosohemoglobin and autoregulation of blood flow through hypoxic vasodilation, and pathological effects of nitrosylation including inhibition of critical vasodilator enzymes; and discuss the intersection of NO source and dose with redox environment, in determining the effects of protein nitrosylation.
This letter is meant to inform the community of pediatricians/pediatric intensivists that we suspect SARS-CoV-2 to cause life-threatening bronchiolitis in infants and we therefore suggest maintaining a high level of suspicion of COVID-19, irrespective of an initially negative SARS-CoV-2 RT-PCR testing, when other causes of bronchiolitis are unidentifiable in young children.
Asthma is a disease characterized by reversible bronchoconstriction, but some subjects develop fixed airflow obstruction (FAO). Subjects with FAO present more asthma symptoms and may have increased sedentary behavior; however, the effect of FAO on aerobic fitness and physical activity levels (PAL) remains poorly understood. Aim: To compare adolescents with asthma and FAO and adolescents with asthma without FAO in terms of aerobic fitness, PAL, muscle strength, and health-related quality of life (HRQoL). Methods: This cross-sectional study included adolescents with asthma, both sexes, and aged 12 to 18 years. They were divided into 2 groups: FAO and non-FAO groups. The adolescents were diagnosed with asthma in accordance with the Global Initiative for Asthma guidelines and underwent optimal pharmacological treatment for at least 12 months. FAO was diagnosed when FEV1/FVC ratio was below the lower limit of normal range after optimal treatment. Aerobic fitness, PAL, peripheral and respiratory muscle strength, and HRQoL were evaluated. Results: No significant differences were observed between FAO and non-FAO groups regarding the peak oxygen uptake (34.6±8.5 vs. 36.0±8.4 mLO2/min/kg), sedentary time (578±126 vs. 563±90 min/day), upper limb muscle strength (29.1±5.9 vs. 28.1±5.7 kgf), lower limb muscle strength (42.8±8.6 vs. 47.6±9.6 kgf), or HRQoL (5.1±1.3 vs. 4.7±1.4 score) (p>0.05). However, the FAO group exhibited a higher maximal expiratory pressure than did the non-FAO group (111.5±15.5 vs. 101.5±15.0 cmH2O, respectively). Conclusion: Our results suggest that FAO does not impair aerobic fitness, PAL, peripheral muscle strength, or HRQoL in adolescents with asthma. Furthermore, adolescents with asthma were physically deconditioned.
Introduction: The Lung Clearance Index (LCI) derived from the multiple-breath washout test (MBW), is both feasible and sensitive to early lung disease detection in young children with cystic fibrosis and asthma. The utility of LCI has not been studied in children with sickle cell disease (SCD). We hypothesized that children with SCD, with or without asthma or airway hyper reactivity (AHR), would have an elevated LCI compared to healthy controls. Methods: Children with SCD from a single center between the ages of 6-18 years were studied at baseline health and completed MBW, spirometry, plethysmography and blood draws for serum markers. Results were compared to healthy controls of similar race, age and gender. Results: Control subjects (n=35) had a significantly higher daytime oxygen saturation level, weight and body mass index (BMI) but not height compared to subjects with SCD (n=34). Total Lung Capacity(TLC) z-scores were significantly higher in the healthy controls compared to those with SCD (0.87 (1.13), 0.02 (1.27), p=0.005) while differences in Forced Expiratory Volume in 1 second (FEV1) z-scores approached significance (0.26 (0.97), -0.22 (1.09), p=0.055). There was no significant difference in LCI among the comparison groups (7.29 (0.72), 7.40 (0.69), p=0.514). Conclusion: LCI did not differentiate SCD from healthy controls in children between the ages of 6 and 18 years at baseline health. TLC may be an important pulmonary function measure to follow longitudinally in the pediatric SCD population.
The first drug specific for cystic fibrosis (CF) was approved in 1993, and since then several other drugs have been approved. Median predicted survival in people with CF has improved from approximately 30 years to 44.4 years over that same period. In 2020, highly-effective modulators of the cystic fibrosis transmembrane conductance regulator became available to approximately 90% of people with CF ages 12 years and older. These transformative therapies will surely reduce morbidity and further extend longevity. The drug development pipeline is filled with therapies that address most aspects of CF disease. As survival and CF therapies have advanced, and the complexity of CF care increases, the process of drug development has become more sophisticated. In addition, detecting meaningful changes in clinical outcomes has become more difficult as the health status of people with CF improves. Design of clinical trials in CF has become more complex, and innovative approaches are required to continue to advance drug development. This review provides a general overview of drug development from the pre-clinical phase through Phase IV. Special considerations with respect to CF are integrated into the discussion of each phase of drug development. The dawn of a new era has arrived for people with CF. As CF care evolves, drug development must continue to evolve as well, until a one-time cure is available to all people with CF.
Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.
To the editor, Chronic eosinophilic pneumonia (CEP) is an idiopathic disease rarely reported in children1,2. It typically occurs in non-smoking, middle age females and the diagnosis requires exclusion of systemic or primary eosinophilic lung diseases1,2. The triad of pulmonary symptoms (usually for >2 weeks), abnormal chest radiographic findings and eosinophilia in the blood and/or pulmonary tissue in the absence of an alternative etiology is highly suggestive of CEP. Patients may present with cough (90-93%) dyspnea (50-90%), fever (77-87%), night sweats (23%), weight loss (57-75%), rhinitis or sinusitis (6-24%), chest pain (8-16%), hemoptysis (8-10%), and weakness/fatigue1,2. An asthma phenotype is present in roughly a third to 3/4 of patients. Bilateral peripheral consolidative infiltrates are seen on chest radiograph (CXR) with computed tomography (CT) showing peripheral airspace disease and reactive hilar adenopathy1,2. Peripheral eosinophilia is almost universal with cell counts routinely higher than 1000/mm3 and more than half of patients also have an elevated IgE2. Eosinophilia on the bronchoalveolar lavage (BAL) ranges from 12 to 95% with a mean of 58%2. The triad of pulmonary symptoms, radiographic findings and eosinophilia in CEP typically respond to prednisone within a few days2. Initial doses range from 0.5 to 1mg/kg/day and may be tapered after clinical/radiographic improvement. Duration of therapy depends on the response and is highly variable, with a mean of 19 months but a range of 0.5 to 96 months1. Relapse is common, occurring in up 50% of patients2. While the pathogenesis of CEP is not fully understood, the underlying mechanism undoubtedly involves eosinophils and likely shares inflammatory pathways with asthma, which is why it may be amenable to treatment with novel biologic therapies approved for asthma. Although there are case reports of patients with CEP who were treated with either omalizumab or mepolizumab, there are no reports of treatment with dupilumab3. However, there is a report of a patient possibly experiencing CEP as a consequence of dupilumab4. We present the case of an 11-year-old, previously healthy, African American female who presented with fever, cough, dyspnea, chest pain and decreased appetite of 3 months duration. Her past medical history was significant for pneumonia three months prior that failed to resolve with antibiotics. She was subsequently prescribed albuterol and treated as an outpatient with a working diagnosis of asthma. Her symptoms persisted and she was ultimately hospitalized with chronic pneumonia of unclear etiology. Her family and social histories were unremarkable. She strongly denied vaping or inhalant abuse. Her physical exam was remarkable for bilateral coarse crackles, signs of respiratory distress and reproducible chest pain. Her CXR showed bilateral consolidative opacities and her CT demonstrated bilateral lymphadenopathy and multilobar consolidation (see Figures 1 &2). Her initial lab work was remarkable for a white blood cell count of 10,000/µL (3.84-9.84/µL) with 10% (0-4%) peripheral eosinophilia, erythrocyte sedimentation rate of 103 mm/hr (0-15mm/hr), and C reactive protein of 7mg/dL (0.00-0.50mg/dL). She was treated with 14 days of antibiotics without clinical improvement. During the course of follow up her FEV1 declined > 35% and she developed a severe persistent asthma phenotype. She was evaluated for tuberculosis, allergic bronchopulmonary aspergillosis, helminth infection, eosinophilic granulomatosis with polyangitis, sarcoidosis, and immunodeficiency however her work up was negative. She underwent bronchoscopy, which demonstrated significant bilateral lower airway casts that were 93% eosinophilic. She was treated with high dose prednisone for 4 weeks and improved for a few months, however her symptoms returned. She continued oral prednisone intermittently for approximately 22 months without improvement and was deemed refractory to therapy. Repeat imaging during that time demonstrated persistent opacities and she developed bronchiectasis. Repeat bronchoscopies revealed return of mucoid impactions. Throughout her course, she continued to have eosinophilia in the blood (ranging from 0.4 to 13%) and on BAL (ranging from 9-93%). She was then treated with pulse methylprednisolone and daily cyclosporine in an attempt to gain clinical remission which resulted in modest improvement of symptoms. She continued daily cyclosporine with the addition of dupilumab every 2 weeks for 6 months. Following the addition of dupilumab significant clinical and radiographic improvement were noted within 2 weeks. Her cyclosporine was subsequently weaned without recurrence of symptoms and she remains symptom free with marked improvement in her Chest X-ray findings for over 12 months on subcutaneous dupilumab injections q 2 weeks. Dupilumab is an injectable humanized IgG4 monoclonal antibody, approved for home use in patients with eosinophilic or steroid dependent asthma, which targets IL-4α receptors and inhibits IL-4 and IL-13 binding. It has been shown to reduce the frequency of asthma exacerbations, improve FEV1 and reduce oral steroid use in patients with severe asthma5. This is the first report of dupilumab as a therapy to treat CEP and the first report of monoclonal antibody therapy to treat CEP in a pediatric patient. Dupilumab may be an alternative for CEP that is refractory to corticosteroids or that requires prolonged therapy. It may also be a more convenient therapy compared to other monoclonal antibodies available to patients because it can be administered at home. References1. Jederlinic PJ, Sicilian L, Gaensler EA. 1988. Chronic eosinophilic pneumonia. A report of 19 cases and a review of the literature. Medicine (Baltimore). 67(3):154-162.2. Marchand E, Reynaud-Gaubert M, Lauque D, Durieu J, Tonnel AB, Cordier JF. 1998. Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62 cases. The groupe d'etudes et de recherche sur les maladies "orphelines" pulmonaires (germ"o"p). Medicine (Baltimore). 77(5):299-312.3. Lin RY, Santiago TP, Patel NM. 2019. Favorable response to asthma-dosed subcutaneous mepolizumab in eosinophilic pneumonia. J Asthma. 56(11):1193-1197.4. Menzella F, Montanari G, Patricelli G, Cavazza A, Galeone C, Ruggiero P, Bagnasco D, Facciolongo N. 2019. A case of chronic eosinophilic pneumonia in a patient treated with dupilumab. Ther Clin Risk Manag. 15:869-875.5. Castro M, Rabe KF, Corren J, Pavord ID, Katelaris CH, Tohda Y, Zhang B, Rice MS, Maroni J, Rowe P et al. 2020. Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma. ERJ Open Res. 6(1).
We read the letter to the editor “B-lines score: artifacts as a sign of neonatal specific disease?” by Quarato et al. and we are pleased by the interest aroused by our article “Neonatal lung ultrasonography score after surfactant in preterm infants: A prospective observational study” published on your journal. This study included preterm neonates with respiratory distress syndrome (RDS), requiring non-invasive ventilation and surfactant. The aim of our citated study was to asses changes of a validated neonatal lung ultrasonography score (nLUS) after surfactant treatment. Our data demonstrate a lowering of the nLUS 2h and 12h after surfactant treatment. In their letter to the editor Quarato et al. expressed criticism about the nLUS score validation and about the utility of the Lung Ultrasound (LUS) as a diagnostic tool. They conclude that “LUS can be used only for diagnosing minimal pleural effusion and, at least, as complementary imaging, in addiction to chest radiographs (CR), for monitoring the reduction of subpleural pneumonitic consolidations under therapy”. Our citated study hasn’t focused on validation of the nLUS score or on LUS as a diagnostic tool for neonatal RDS, so we don’t get how Quarato’s concerns can be addressed to our paper. Nevertheless, finding the debate about nLUS or LUS in the neonatal field an occasion to promote an improving in the care of the preterm babies, we will discuss objections raised in Quadrato’s work, point by point.
Objectives: To evaluate the risk factors of recurrent pulmonary exacerbation and poor prognosis in children with idiopathic pulmonary hemosiderosis (IPH). Methods: In this multicenter study, 54 patinets with diagnosis of IPH included. Medical records were retrospectively reviewed from three tertiary care hospitals between 1979 and 2019. Also, current information and the long-term progress of patients was determined by contacting the families by telephone. Results: A total of 54 children were included. The median age of onset of symptoms was 4.5 ± 3.8 years. The median time from onset to diagnosis was 0.9 years ± 2.2. The mean number of recurrent episodes per child in the recurrence-positive group was 3.55 (1-15). Univariate analysis demonstrated that patients presenting with hypoxia or requiring transfusion at the time of presentation had significantly more recurrence episodes (P=0.002). Multivariate analysis showed that the presence of hypoxia at the time of initial presentation was a significant independent predictor of recurrent episodes (P=0.027). The median follow-up was 3.3 ± 4.8 years (0.75 months-27 years). There was a significant relationship between the presence of hypoxia, transfusion history, ANA positivity, and elevated transaminases at the time of initial evaluation and treatment response. Conclusions: The present study provides important information on the clinical course and outcome of pediatric IPH, and substantial information regarding factors that affect recurrent exacerbations and prognosis. Demonstrating of hypoxia as an independent risk factor in recurrence episodes could be guide physicians in the planning of treatment strategies.