Atypical pulmonary metastases in children: the spectrum of radiologic findings.

Pulmonary nodules present a diagnostic challenge when they appear as atypical metastases in pediatric oncology patients. Chest computed tomography (CT) is the primary imaging modality for assessing lung nodules. In pediatric populations, Wilms tumor and osteosarcoma are the cancers most likely to produce pulmonary metastasis, both typical and atypical. This pictorial essay provides a thorough description of the specific radiologic features of atypical pediatric pulmonary metastases, and their pathogenesis and differential diagnosis. We also address diagnostic approaches to incidental lung nodules in healthy children found in the literature. Our aim is to help radiologists identify atypical lung metastases on CT, ensuring that children receive prompt, and potentially lifesaving, treatment.

Novel NCF2 Mutation Causing Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in the NADPH oxidase complex. Mutations in NCF2 encoding the cytosolic factor p67phox result in autosomal recessive CGD. We describe three patients with a novel c.855G>C NCF2 mutation presenting with diverse clinical phenotype. Two siblings were heterozygous for the novel mutation and for a previously described exon 8-9 duplication, while a third unrelated patient was homozygous for the novel mutation. Mutation pathogenicity was confirmed by abnormal DHR123 assay and absent p67phox production and by sequencing of cDNA which showed abnormal RNA splicing. Clinically, the homozygous patient presented with suspected early onset interstitial lung disease and NCF2 mutation was found on genetic testing performed in search for surfactant-related defects. The two siblings also had variable presentation with one having history of severe pneumonia, lymphadenitis, and recurrent skin abscesses and the other presenting in his 30s with discoid lupus erythematosus and without significant infectious history. We therefore identified a novel pathogenic NCF2 mutation causing diverse and unusual clinical phenotype.

The Effect of a 30-Min Water-Pipe Smoking Session on Cognitive Measures and Cardio-Pulmonary Parameters.

INTRODUCTION: One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion. METHODS: A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes. RESULTS: Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25-75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively). CONCLUSIONS: One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS. IMPLICATIONS: One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.

Incidence of congenital thoracic malformations detected by prenatal ultrasound.

BACKGROUND: The increased and earlier use of prenatal ultrasound has facilitated the detection of congenital thoracic malformations (CTMs). Our Pediatric Pulmonology Institute follows an increasing number of patients with CTMs. Thus, we aimed to evaluate and describe prenatal sonographic findings of CTM, and to estimate changes in detection rates of CTMs over a period of 16 years. METHODS: A retrospective, cross-section analysis of prenatal ultrasound (US) screening tests carried out in a large community-based clinic, comparing two periods: 2001-2007 and 2007-2017. RESULTS: A total of 34 716 prenatal US were performed at a median gestational age of 15.4 weeks (range, 11.6-23.9) and 15.7 weeks (range, 12-33.6) in 2001-2007 and 2007-2017, respectively. In 2001-2007, 12 016 prenatal US tests detected 19 CTMs, compared to 30 CTMs in 22 700 tests in 2007-2017. Detection rates did not change (1.58/1,000 in 2001-2007 versus 1.32/1,000 in 2007-2017, P = 0.64). The most common abnormality was congenital pleural effusion (CPE) (17 cases, 34.7%), followed by congenital pulmonary airway malformation) and congenital diaphragmatic hernia; 13 cases each, 26.5%. Twenty CTMs, mainly congenital diaphragmatic hernia and CPE, were associated with other fetal lesions. CONCLUSIONS: Congenital diaphragmatic hernia and CPE tend to appear with multiple lesions and warrant further attention. The incidence rates stayed stable when comparing the last decade to previous years. Thus, the increased referral of CTM can be attributed to an increase in the number of prenatal screening studies performed, rather than a true higher incidence.

Bronchoscopy and Bronchoalveolar Lavage in the Diagnosis and Management of Pulmonary Infections in Immunocompromised Children.

BACKGROUND: Immunocompromised children are at high risk of rapid deterioration and of developing life-threatening pulmonary infections. Etiologies in this setting are diverse, including those that are infectious and noninfectious, and many etiologies may coexist. Accurate diagnosis is required for the rational use of medications. Fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) can identify infectious causes in this population. OBJECTIVES: The aims of this study were to evaluate diagnostic rate, safety, and changes in treatment following FOB with BAL, when applied with advanced laboratory diagnostic techniques. PATIENTS AND METHODS: We reviewed the records of children who underwent FOB with BAL during the period spanning from 2006 to 2014 in the Hematology-Oncology Department. BAL samples were processed in microbiology, virology, cytology, and molecular laboratories. RESULTS: Antimicrobials were initiated in 91 of 117 children. BAL yielded an infectious etiology in 55 episodes. Management was altered in 74 patients following a positive (40/55) or a negative (30/54) result (4 patients had missing data). No severe complications associated with the procedures occurred. CONCLUSIONS: Most immunocompromised patients with pulmonary manifestations are treated empirically with multiple medications. Evaluation FOB/BAL is a useful diagnostic tool, and seems to have changed the course of therapy in more than half of patients, by initiation or cessation of treatment. FOB/BAL is a safe diagnostic tool for the evaluation of pulmonary manifestations in this setting.

Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa.

INTRODUCTION: CF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy. PURPOSE: Our aim was to assess whether spirometry, lung clearance index and circulating inflammatory markers differ between on/off treatment periods. MATERIALS AND METHODS: A prospective pilot study evaluating CF patients treated with TIP, on two consecutive months (on/off) therapy. The evaluations were performed at the end of a month off therapy (1-2 days before the initiation of TIP) and after 28 days of treatment with TIP (1-2 days after the end of the treatment cycle). RESULTS: Nineteen CF patients (10 males) with a mean age of 18.7±9.7 years and BMI (body mass index) of 19.62±3.53 kg/m2 were evaluated. After a month off treatment with TIP, spirometry parameters and lung clearance index remained unchanged. IL-6 increased significantly (p=0.022) off treatment. There was a non-significant change in the other inflammatory cytokines off therapy [hs-CRP, IL-8,TNF-α, α1-antitrypsin (α1AT) and neutrophilic elastase]. CONCLUSIONS: The results of lung function parameters support the relative stability of CF patients during the month off therapy; however, the difference in serum IL-6 raises the possibility of ongoing higher degrees of inflammation during the month off therapy with TIP. The small sample size and the multiple parameters evaluated preclude firm conclusions; therefore, larger multicenter studies are needed to assess the on/off treatment strategy.

Factors Associated with Recurrence of Tracheoesophageal Fistula.

BACKGROUND: Recurrence of tracheoesophageal fistula (TEF) is reported in 8-20% patients. Factors that may influence recurrence of fistula beyond the postoperative period are not clear. OBJECTIVES: To evaluate possible factors associated with recurrence of TEF beyond the immediate postoperative period. METHODS: A single center, retrospective comparison of patients with and without recurrence of TEF was conducted. Medical records of patients previously operated for TEF who were followed in our pediatric pulmonary institute between January 2007 and December 2016 were reviewed. RESULTS: The medical records of 74/77 patients previously operated for TEF were evaluated. Nine patients (12%) had a recurrence of TEF and 65 did not. These groups had similar age and gender distribution and similar prevalence of VACTERL association. In addition, they had similar length of atretic gap, rates of thoracoscopic surgery, rates of prolonged need for respiratory assistance post-surgery, and frequency of gastrointestinal symptoms. Notably, the patients who had recurrent TEF had significantly more hospitalizations for respiratory symptoms (P = 0.011) and significantly more episodes of clinical bronchiolitis per patient (P < 0.0001). In addition, the patients with recurrent TEF had significantly more episodes of positive polymerase chain reaction for viruses (P = 0.009). CONCLUSIONS: Hospitalizations for respiratory symptoms as well as clinical and/or viral bronchiolitis are associated with recurrence of TEF. Even though cause and effect cannot be established, these patients should undergo meticulous evaluation for the possibility of recurrence of TEF.

Cleaning and infection control of airway clearance devices used by CF patients.

Respiratory treatment for cystic fibrosis (CF) patients includes use of respiratory devices. Contamination of airway clearance devices has not been adequately explored. We aimed to determine whether airway clearance devices are contaminated after use and whether cleaning guidelines for nebulizers are as effective for airway clearance devices. Patients brought their airway clearance devices to the clinic. Swabs from the devices were taken before and after cleaning and were cultured for bacterial counts. Total colony-forming units (CFU) was determined, and predominant colonies were identified using Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry technology. Thirty devices were collected from 23 patients. Most of the devices (28/30) were contaminated when brought to the clinic. Complete bacterial eradication was achieved in 15 (50%) samples and partial eradication in 9 (30%). The cleaning was totally ineffective in four samples. Median CFU decreased significantly from 1250 (IQR 25-75% 175-10.000) to 0 (IQR 25-75% 0-700) before and after cleaning ( p < 0.0001). The predominant organisms were identified in five samples only, and there was no concordance with sputum culture results. Airway clearance devices are contaminated after use, and appropriate cleaning can reduce contamination. The effect on disease progression in CF patients is unclear. There is a need for infection prevention and control guidelines for the growing number of respiratory devices.

Systematic Analysis of CCNO Variants in a Defined Population: Implications for Clinical Phenotype and Differential Diagnosis.

Reduced generation of multiple motile cilia (RGMC) is a novel chronic destructive airway disease within the group of mucociliary clearance disorders with only few cases reported. Mutations in two genes, CCNO and MCIDAS, have been identified as a cause of this disease, both leading to a greatly reduced number of cilia and causing impaired mucociliary clearance. This study was designed to identify the prevalence of CCNO mutations in Israel and further delineate the clinical characteristics of RGMC. We analyzed 170 families with mucociliary clearance disorders originating from Israel for mutations in CCNO and identified two novel mutations (c.165delC, p.Gly56Alafs*38; c.638T>C, p.Leu213Pro) and two known mutations in 15 individuals from 10 families (6% prevalence). Pathogenicity of the missense mutation (c.638T>C, p.Leu213Pro) was demonstrated by functional analyses in Xenopus. Combining these 15 patients with the previously reported CCNO case reports revealed rapid deterioration in lung function, an increased prevalence of hydrocephalus (10%) as well as increased female infertility (22%). Consistent with these findings, we demonstrate that CCNO expression is present in murine ependyma and fallopian tubes. CCNO is mutated more frequently than expected from the rare previous clinical case reports, leads to severe clinical manifestations, and should therefore be considered an important differential diagnosis of mucociliary clearance disorders.