Vaping-Associated Lung Injury During COVID-19 Multisystem Inflammatory Syndrome Outbreak.

BACKGROUND: E-cigarette or vaping product use-associated lung injury (EVALI) is a complex inflammatory syndrome predominantly seen in adolescents and young adults. The clinical and laboratory profile can easily mimic infectious and noninfectious conditions. The exclusion of these conditions is essential to establish the diagnosis. Recently, the novel coronavirus disease 2019 (COVID-19) pandemic introduced the multisystem inflammatory syndrome in children (MIS-C). MIS-C knowledge is evolving. The current criteria to establish the diagnosis are not specific and have overlapping features with EVALI, making the accurate diagnosis a clinical challenge during continued COVID-19 transmission within the community. CASE REPORT: Three young adults evaluated at our emergency department for prolonged fever and gastrointestinal and respiratory symptoms were initially assessed for possible MIS-C due to epidemiologic links to COVID-19 and were eventually diagnosed with EVALI. The clinical, laboratory, and radiologic characteristics of both entities are explored, as well as the appropriate medical management. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Physician awareness of overlapping and differentiating EVALI and MIS-C features is essential to direct appropriate diagnostic evaluation and medical management of adolescents and young adults presenting with systemic inflammatory response during the unfolding pandemic of COVID-19.

Pediatric patients with chronic cough and recurrent croup: the case for a multidisciplinary approach.

OBJECTIVE: To evaluate the results of our multidisciplinary approach to recurrent croup and chronic cough. METHODS: Retrospective chart review of all patients with recurrent croup and chronic cough managed at a tertiary care children's hospital by our Comprehensive Airway, Respiratory, and Esophageal (CARE) Team. Charts were reviewed for all patients who carried a diagnosis of recurrent croup or chronic cough. Patients were excluded if they did not receive a full workup, including micro-direct laryngoscopy, flexible and/or rigid bronchoscopy, bronchioalveolar lavage (BAL), and upper endoscopy with biopsies. We reviewed the records for the presence of gastrointestinal complaints, abdominal pain and failure to thrive (FTT) and compared the children with documented esophagitis to the remaining children. RESULTS: Forty patients met inclusion criteria. 53% had airway abnormalities; the most common was tracheomalacia, followed by enlarged adenoids. 38% had esophagitis (group 1) while 62% had normal esophageal biopsies (group 2). Among the children in group 1, 27% met criteria for eosinophilic esophagitis (>15 eosinophils per high powered field). There was no significant difference between groups 1 and 2 based on the presence of gastrointestinal complaints, abdominal pain and/or FTT (p>0.05). There was no significant difference between the groups based on the location or presence of an airway abnormality (p>0.05). CONCLUSIONS: Children with recurrent croup and chronic cough may benefit from a multidisciplinary approach to management. Our CARE Team approach led to a specific diagnosis in almost 95% of patients.

Heterogeneity of lower airway inflammation in children with severe-persistent asthma.

RATIONALE: The treatment of children with severe-persistent asthma remains problematic. Recent studies suggest that stratification of this cohort by inflammatory type may be useful in designing effective treatment strategies. In this study, we examined the inflammatory profile in bronchoalveolar lavage fluid from children with severe-persistent asthma and compared this profile with serum IgE levels. METHODS: The inflammatory profile in the bronchoalveolar fluid from 32 children who met criteria for severe-persistent asthma as defined by the Severe Asthma Research Program (SARP) were analyzed retrospectively. Inflammatory patterns were classified as neutrophilic, eosinophilic, mixed, or pauci-granulocytic. Serum total IgE was measured prior to bronchoscopy and determined by ELISA at each hospital's lab by standard procedures. RESULTS: The most common pattern of inflammation in this cohort was neutrophilic (37.5%) followed by eosinophilic (28.1%), mixed (21.9%), and pauci-granulocytic (11.1%). The odds ratio of an eosinophilic BAL pattern for patients with an elevated serum IgE was 4.67 (CI 0.78-28, P = 0.12). A correlation between serum IgE levels and BAL eosinophil percentages was present (P = 0.04). CONCLUSIONS: To our knowledge, ours is one of few studies to systematically investigate the pattern of lower airway inflammation in children with severe-persistent asthma. Our results differ from a recent investigation in children, showing more heterogeneity and a greater proportion of neutrophilic inflammation. Further investigation is required to determine whether specific inflammatory patterns are associated with specific etiologies, and whether individualized therapy is warranted.

Fungal sensitization in childhood persistent asthma is associated with disease severity.

RATIONALE: Recent observations, especially in adults, suggest that asthma severity may be associated with fungal sensitization. Other studies suggest that some patients with severe asthma and fungal sensitization may benefit from anti-fungal therapy. Currently, the prevalence of fungal sensitization among children with severe asthma is not well characterized. METHODS: We determined prevalence of fungal sensitization among children with moderate to severe persistent asthma and compared clinical characteristics between sensitized and non-sensitized children, including asthma severity, serum immunoglobulin E, and pulmonary function. RESULTS: Of the 64 children enrolled, 25 (39%) had evidence of sensitization to one or more fungi. Nineteen of 25 (76%) children with fungal sensitization were categorized as severe persistent compared to 13 of 39 (33%) children without evidence of fungal sensitization (odds ratio = 6.33, 95% confidence interval 2.04-19.68, P = 0.0014). Of 32 severe persistent asthmatics, 19 (59%) demonstrated evidence of fungal sensitization. Serum immunoglobulin E was significantly higher (P < 0.001), and pulmonary function (including FEV1, FEV1/FVC, and FEF25-75%) significantly lower in the fungal-sensitized patients (P = 0.016, 0.0004, and 0.002, respectively). Bronchial biopsy of sensitized children revealed basement membrane thickening and eosinophil infiltration. CONCLUSIONS: Fungal sensitization in children with persistent asthma is associated with disease severity. Almost 60% of our severe persistent asthma patients had evidence of fungal sensitization and, based on our previous studies, may be potential candidates for anti-fungal therapy.

Methylxanthine inhibit fungal chitinases and exhibit antifungal activity.

Chitinases are necessary for fungal cell wall remodeling and cell replication. Methylxanthines have been shown to competitively inhibit family 18 chitinases in vitro. We sought to determine the effects of methylxanthines on fungal chitinases. Fungi demonstrated variable chitinase activity and incubation with methylxanthines (0.5-10 mM) resulted in a dose-dependent decrease in this activity. All fungi tested, except for Candida spp., demonstrated growth inhibition in the presence of methylxanthines at a concentration of 10 mM. India ink staining demonstrated impaired budding and decreased cell size for methylxanthine-treated Cryptococcus neoformans. C. neoformans and Aspergillus fumigatus treated with pentoxifylline also exhibited abnormal cell morphology. In addition, pentoxifylline-treated C. neoformans exhibited increased susceptibility to calcofluor and a leaky melanin phenotype consistent with defective cell wall function. Our data suggest that a variety of fungi express chitinases and that methylxanthines have antifungal properties related to their inhibition of fungal chitinases. Our results highlight the potential utility of targeting chitinases in the development of novel antifungal therapies.

Infectious Chlamydia pneumoniae is associated with elevated interleukin-8 and airway neutrophilia in children with refractory asthma.

BACKGROUND: Neutrophilic asthma is thought to be less responsive than eosinophilic asthma to anti-inflammatory therapies including corticosteroids. Chlamydia pneumoniae has been implicated in asthma, possibly by induction of interleukin (IL-8). We hypothesized that IL-8 is increased in the bronchoalveolar lavage (BAL) fluid from children with asthma and C. pneumoniae. METHODS: BAL fluid was analyzed for C. pneumoniae and IL-8 using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay from 2 asthma patient populations in the Bronx, NY and Massachusetts with an average age of 8 and 8.7 years old, respectively. For comparison, samples were also analyzed for C. trachomatis and Mycoplasma 16s DNA. RESULTS: Of 18 Bronx samples analyzed, 6 (33%) were PCR-positive for C. pneumoniae, 10 (56%) for C. trachomatis, and 8 (44%) for Mycoplasma 16s DNA. IL-8 from C. pneumoniae-positive samples was 3.3-fold higher compared with negative samples (P = 0.003). There was no difference between patients tested for C. trachomatis or Mycoplasma. Of 84 Massachusetts samples analyzed, 42 (50%) were PCR-positive for C. pneumoniae, 42 (50%) for C. trachomatis, and 13 (16%) for Mycoplasma. IL-8 concentration from C. pneumoniae-positive samples was 10.49-fold higher compared with negative samples (P = 0.0001). As in the Bronx cohort, there were no differences between patients tested for C. trachomatis or Mycoplasma. Lastly, BAL neutrophilia predicted the presence of C. pneumoniae but not Mycoplasma or C. trachomatis. CONCLUSIONS: Children with asthma who were PCR-positive for C. pneumoniae demonstrated elevated concentrations of IL-8 and neutrophils in BAL fluid compared with similar patients who were positive for C. trachomatis or Mycoplasma organisms, but PCR-negative for C. pneumoniae. Undiagnosed C. pneumoniae infection in children may therefore contribute to poorly controlled asthma via induction of IL-8.

CHIT1 mutations: genetic risk factor for severe asthma with fungal sensitization?

Fungi can exacerbate symptoms in patients with asthma. To our knowledge, genetic risk factors for fungal-associated asthma have not been described. We present here the cases of 6 children who carried the diagnosis of severe asthma with fungal sensitization, 3 of whom were treated with and responded clinically to itraconazole therapy. All 6 patients were heterozygous for a 24-base pair duplication in the CHIT1 gene, which has been associated with decreased levels of circulating chitotriosidase and susceptibility to fungal infection.

Severe asthma with fungal sensitization in a child: response to itraconazole therapy.

People with severe asthma with fungal sensitization may represent an underdiagnosed subset of patients with refractory disease. It is important to know that such patients may benefit from adjunct treatment with antifungal agents. We describe here the case of a child with refractory asthma, persistent airway obstruction, a serum immunoglobulin E level of >20000 IU/mL, and severe eosinophilic airway infiltration. Although he did not meet diagnostic criteria for allergic bronchopulmonary aspergillosis, he demonstrated evidence of sensitization to several fungi and responded dramatically to the addition of itraconazole therapy. We also discuss emerging hypotheses regarding fungal-induced asthma.

Management of severe tracheal stenosis using flexible bronchoscopy and impulse oscillometry.

Although rigid bronchoscopy is the procedure of choice for interventional procedures of the proximal airway, flexible bronchoscopy can be used when lesions are not accessible by rigid equipment. We present an adolescent patient with tracheal stenosis whose airway was inaccessible through rigid bronchoscopy and thus required flexible bronchoscopy for all therapeutic procedures, including a stent placement. In addition, we describe our use of impulse oscillometry to monitor stent patency.

Hereditary hemorrhagic telangiectasia and juvenile polyposis: an overlap of syndromes.

Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu syndrome) is a syndrome characterized by multiorgan telangiectases and arteriovenous malformations. A subset of patients with a mutation in the MADH4 gene on chromosome 18 exhibits an overlapping syndrome of HHT and juvenile polyposis (JPS). We present one such family. Genetic testing is warranted when either HHT or JPS is diagnosed, as early recognition of this syndrome overlap allows appropriate management of these patients.