Hyperthyroidism in a 15-year-old adolescent treated with Dupilumab for severe allergic asthma and atopic dermatitis.

Dupilumab is a biologic, acting on IL-4 and IL-13 pathways. Dupilumab has a pediatric indication for treating severe asthma and atopic dermatitis. We report a pediatric case concerning paucisymptomatic, transient, and self-resolving hyperthyroidism. The updated literature includes the case of an adult patient who reported with hyperthyroidism, which was transient and self-resolving. Despite that these cases were transient and self-resolving, we would suggest that thyroid function assessment could be included in the follow-up of patients treated with Dupilumab. Dupilumab discontinuation is not required pending endocrinological assessment, mainly if there is an optimal clinical response to the biologic.

Steroid-sparing effect of mepolizumab in children with severe eosinophilic nonallergic asthma.

BACKGROUND: Asthma is characterized by a chronic airway inflammation, usually sustained by type 2 immunity. Bronchial and peripheral eosinophilia are biomarkers for type 2 asthma. Biologicals are the most effective treatment for severe asthma at present. Mepolizumab is an antagonist of interleukin-5 (IL-5), the most relevant cytokine involved in eosinophilia. OBJECTIVE: This case report evaluated the effectiveness of mepolizumab in two girls with severe eosinophilic non-allergic asthma. MATERIALS AND METHODS: Two female children with severe eosinophilic nonallergic asthma were treated with mepolizumab for two years. Clinical findings, lung function, peripheral eosinophils, asthma control, and bronchial endoscopy were performed. RESULTS: Biologicals reduced the eosinophilia, asthma exacerbations, and improved lung function in both patients. The treatment was also safe and well-tolerated. CONCLUSION: Mepolizumab represents an effective therapeutic option in the management of severe pediatric asthma.

Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome.

OBJECTIVES: Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib. METHODS: We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis. RESULTS: We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease. CONCLUSIONS: We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.

Imatinib melylate as second-line treatment of bronchiolitis obliterans after allogenic hematopoietic stem cell transplantation in children.

BACKGROUND: The onset of bronchiolitis obliterans (BO) as a pulmonary manifestation of chronic graft vs host disease dramatically changes the prognosis of children undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the overall survival (OS) of children with BO treated with imatinib mesylate (IM). METHODS: This study included children who underwent allo-HSCTs between January 2000 and December 2016. RESULTS: Among 345 patients who underwent HSCTs, 293 were evaluable for BO and 26 (8.9%) developed BO. The cumulative incidence of BO was 4.8% (95% confidence interval [CI], 2.8-7.5) at 1 year and 7.7% (95% CI, 5.1-11.1) at 3 years after transplantation. In the group of HSCTs (n = 67) complicated by chronic GvHD (c-GVHD), the incidence rate of BO was 38.8%. In total, 96.1% of patients with BO had c-GvHD worse than moderate grade, which was present in 70.7% of patients without BO (P = .011). The mortality rates were 46.1% in the BO group and 27.4% in the group without BO. Half of the patients with BO (n = 13) received IM, and the overall response rate was 76.9%. Four years after HSCT, OS was 42.6% (95% CI, 18.2-65.3) in the group without IM and 83.3% (95% CI, 27.3-97.5) in the group with IM. CONCLUSIONS: BO after HSCT in the pediatric population has a high incidence and mortality rate. In terms of overall response and tolerability, this study showed relevant improvements in the prognosis of children with BO after the introduction of IM. Further prospective studies among children are needed to confirm these results.

Hyperthyroidism in a 15-year-old adolescent treated with Dupilumab for severe allergic asthma and atopic dermatitis

Dupilumab is a biologic, acting on IL-4 and IL-13 pathways. Dupilumab has a pediatric indication for treating severe asthma and atopic dermatitis. We report a pediatric case concerning paucisymptomatic, transient, and self-resolving hyperthyroidism. The updated literature includes the case of an adult patient who reported with hyperthyroidism, which was transient and self-resolving. Despite that these cases were transient and self-resolving, we would suggest that thyroid function assessment could be included in the follow-up of patients treated with Dupilumab. Dupilumab discontinuation is not required pending endocrinological assessment, mainly if there is an optimal clinical response to the biologic (AU)

Steroid-sparing effect of mepolizumab in children with severe eosinophilic nonallergic asthma

Background: Asthma is characterized by a chronic airway inflammation, usually sustained by type 2 immunity. Bronchial and peripheral eosinophilia are biomarkers for type 2 asthma. Biologicals are the most effective treatment for severe asthma at present. Mepolizumab is an antagonist of interleukin-5 (IL-5), the most relevant cytokine involved in eosinophilia. Objective: This case report evaluated the effectiveness of mepolizumab in two girls with severe eosinophilic non-allergic asthma. Materials and methods: Two female children with severe eosinophilic nonallergic asthma were treated with mepolizumab for two years. Clinical findings, lung function, peripheral eosinophils, asthma control, and bronchial endoscopy were performed. Results: Biologicals reduced the eosinophilia, asthma exacerbations, and improved lung function in both patients. The treatment was also safe and well-tolerated. Conclusion: Mepolizumab represents an effective therapeutic option in the management of severe pediatric asthma (AU)

Mild tracheal compression by aberrant innominate artery and chronic dry cough in children.

BACKGROUND: In children with aberrant innominate artery (AIA) one of the most prevalent respiratory symptom is dry cough. How frequently this mediastinal vessels anomaly, that can induce tracheal compression (TC) of different degree, may be detected in children with chronic dry cough is not known. METHODS: In a 3-year retrospective study, the occurrence of mediastinal vessels abnormalities and the presence and degree of TC was evaluated in children with recurrent/chronic dry cough. RESULTS: Vascular anomalies were detected in 68 out of the 209 children evaluated. A significant TC was detected in 54 children with AIA, in eight with right aortic arch, in four with double aortic arch but not in two with aberrant right subclavian artery. In AIA patients, TC evaluated on computed tomography scans, was mild in 47, moderate in six and severe in one. During bronchoscopy TC increased in expiration or during cough, but this finding was more pronounced in children with right aortic arch and double aortic arch in which a concomitant tracheomalacia was more evident. Comorbidities were detected in 21 AIA patients, including atopy, reversible bronchial obstruction and gastroesophageal reflux. Aortopexy was performed in eight AIA patients, while the remaining AIA patients were managed medically and showed progressive improvement with time. CONCLUSION: Mild TC induced by AIA can be detected in a sizeable proportion of children with recurrent/chronic dry cough. The identification of this anomaly, that may at least partially explain the origin of their symptom, may avoid further unnecessary diagnostic examinations and ineffective chronic treatments.

Clinical, physiologic, and roentgenographic changes after pneumonectomy in a boy with Macleod/Swyer-James syndrome and bronchiectasis.

Macleod/Swyer-James syndrome is an uncommon and complex disease characterized by roentgenographic hyperlucency of one lung or lobe due to loss of the pulmonary vascular structure and to alveolar overdistension. This syndrome seems to be an acquired disease that follows viral bronchiolitis and pneumonitis in childhood. It must be differentiated from many other causes of unilateral lung "transradiancy" on the chest roentgenogram, such as those related to congenital bronchial and/or vascular abnormalities. We here describe an 11-year-old patient with Macleod/Swyer-James syndrome and bronchiectasis resulting in severe recurrent bronchopulmonary infections. Despite the severe impairment of pulmonary function, the patient underwent resection of the right lung with progressive improvement of clinical and physiologic parameters.

Corticosteroids may favor proliferation of thoracic inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumor (IMT) was thought to represent a benign post-infectious or post-inflammatory process cured by surgical resection. However, reports of cases with an aggressive clinical course suggest the need for caution about the prognosis. The treatment of choice is a complete surgical resection, while medical treatment options are limited. Corticosteroid therapy has been used with some success in unresectable lesion. However, rapid progression of lung IMT after prednisone treatment has been reported, raising the hypothesis that corticosteroids may favor a tumultuous proliferation of this lesion, possibly through immunosuppression. We here report a similar observation and suggest that other mechanisms may be involved. A 5-year and 6-month-old boy presented with a 72 hr history of breathlessness, initially responsive to albuterol and prednisone. He represented 15 days later with increasing symptoms despite further prednisone treatment. CT chest scan showed a mass lesion in the tracheal lumen, which on biopsy was found to be an IMT. The possibility that prednisone may have an enhancing effect on IMT cell proliferation is demonstrated through IMT cell culture and discussed.

Tracheal compression by aberrant innominate artery: clinical presentations in infants and children, indications for surgical correction by aortopexy, and short- and long-term outcome.

BACKGROUND: Aberrant innominate artery (AIA) may cause various degrees of tracheal compression (TC). PURPOSE: The aim of this study is to define the clinical manifestations of AIA-induced TC and outcome after aortopexy in infants and older children. METHODS: Children with significant AIA-induced TC were evaluated, and information after surgery or conservative management was obtained by telephonic interview after 1 to 4 years since discharge. RESULTS: Overall, 15 infants (mean age, 8 months; group A) and 13 older children (mean age, 56 months; group B) were evaluated. Although median age at onset of symptoms was comparable in the 2 groups, mean delay to diagnosis was higher in group B (P < .0001). Analysis of the most prevalent symptoms showed that reflex apneas were more frequent in group A (P = .02), whereas chronic "intractable" cough was more frequent in group B (P < .001). Because of the type and severity of symptoms and the degree of TC, 16 patients underwent aortopexy. Follow-up evaluation showed, in all but 1 patient, a significant improvement in symptoms and quality of life, measured by a modified Visick score. CONCLUSIONS: Aberrant innominate artery-TC leads to a variety of respiratory disorders, with a difference in prevalence between infants and older children. When choice of treatment is based on clinical presentation and degree of TC, a good clinical outcome may be obtained also in children in whom aortopexy is indicated, that is, those presenting initially with more severe symptoms.

Recurrent severe lower respiratory tract infections in a child with abnormal tracheal morphology.

Localized recurrent respiratory infections, leading to severe hypoxia in young children without immunological abnormalities or other risk factors, should raise the suspicion of airway structural abnormalities. In a 24-month-old boy, with recurrent severe post-viral wheezing and a history of RSV-induced bronchiolitis and gastro-esophageal reflux, fiberoptic bronchoscopy demonstrated an abnormal morphology of the distal portion of the trachea, ending in four openings. Computed tomography (CT) scans demonstrated the presence of a right tracheal bronchus and an anomalous upper lobar bronchus, originating at the level of the major carina.

Intermittent gaseous bowel distention: atypical sign of congenital tracheoesophageal fistula.

Three girls, 5-, 9-, and 15-year-old, were evaluated for recurrent airway infections and pneumonia. Chest X-rays, which included the upper portion of the abdomen, showed marked gaseous bowels distention, while computed tomography scans of the chest demonstrated the presence of tracheoesophageal fistula (TEF), confirmed by fiberoptic bronchoscopy. Abdominal gaseous distension, a known possible clinical manifestation of TEF in the neonatal period generated by airflow through the fistula into the oesophagus, has not been reported as a clue to the diagnosis in older children. When detected in patients with recurrent respiratory infection, should raise the suspicion of unrecognized TEF.

Gastroesophageal reflux and its clinical manifestation at gastroenteric and respiratory levels in childhood: physiology, signs and symptoms, diagnosis and treatment.

Gastroesophageal reflux (GER) is a physiological process occurring with different frequency and characteristics in healthy infants, children and adults, most episodes being brief and asymptomatic. By contrast, GER disease (GERD) occurs when this normal event results in the occurrence of symptoms/signs or complications involving the upper portion of the gastroenteral tract and the respiratory system. Transient relaxations of the lower esophageal sphincter represent the major mechanism responsible for reflux episodes, possibly associated with gastroesophageal dysfunctional motility, excessive gastric acid secretion or anatomic abnormalities. The diagnosis of GERD, that is, a causal relationship between reflux and GERD symptoms, may be difficult to determine and make clinically, with support needed from diagnostic evaluations, and final confirmation by response to treatment. Management of GER/GERD should follow a stepwise approach: lifestyle modifications, pharmacologic therapy and surgical procedures; some of these steps may occur simultaneously. In children with mild symptoms and without anatomic abnormalities, the initial choice should be lifestyle modifications and pharmacologic therapy with prokinetic agents, antacids and histamine-2-receptor antagonists. For severe GERD, therapeutic options include proton pump inhibitors and antireflux surgery. In determining the best approach for each individual patient, efficacy, safety, morbidity, compliance and cost must be considered.

The lung and the gut: common origins, close links.

Because of the common embryologic origin, alteration of the many factors modulating the development of the alimentary and the respiratory tract often results in structural abnormalities involving the two systems. Indeed, some of the most common embryologic disorders of the airways are frequently associated with anomalies of the gastrointestinal tract. Lung growth occurs as a series of tightly regulated events, depending on a number of factors, including developmental, genetic and environment ones. Abnormalities of any of these factors may causes developmental alterations of the lung leading to a group of disorders termed "bronchopulmonary-foregut malformations". These are usually sporadic, solitary cystic hamartomas, involving conducting airways, arteries, venous drainage, and lung parenchyma, which are now often discovered on routine prenatal sonography. While some lesions may be large and cause serious complications in the foetus or newborn, many will be asymptomatic at birth, raising controversy about management: simple observation or surgery and, if so, at what age? Over the past two decades molecular studies have started to shed light on the complex series of events that control proper formation of the lung, with the hope that a better understanding of the molecular basis of pulmonary maturation will allow the design of new therapeutic strategies.