Non-infectious Pulmonary Complications in Children with Primary Immunodeficiency.

Primary immune deficiency (PID) is a large group of diseases characterized by defective immune function, leading to recurrent infections, and immune dysregulation. Clinical presentations, severity, and complications differ for each disease, based on the components of the immune system that are impacted. When patients with PID present with respiratory symptoms, infections should be initially suspected, investigated, and promptly managed. However, non-infectious complications of PID also frequently occur and can lead to significant morbidity and mortality. They can involve both the upper and lower respiratory systems, resulting in various presentations that mimic infectious diseases. Thus, clinicians should be able to detect these conditions and make an appropriate referral to an immunologist and a pulmonologist for further management. In this article, we use case-based scenarios to review the differential diagnosis, investigation, and multidisciplinary treatment of non-infectious pulmonary complications in patients with primary immune deficiencies.

Unique presentation of late-onset Pneumocystis pneumonia in a pediatric kidney transplant recipient.

BACKGROUND: Restrictive lung disease leading to abnormal lung function in kidney transplant recipients is commonly associated with noninfectious complications or medications used for post-transplant immunosuppression. Herein, we report an interesting case of pediatric kidney transplant recipient with weight loss and abnormal spirometry who was diagnosed to have late-onset Pneumocystis pneumonia. CASE REPORT: A 17-year-old male patient with a history of allergic rhinitis, mild persistent asthma, and deceased donor kidney transplant, performed 18 months prior, presented for routine evaluation of his asthma to the pulmonology clinic. He was clinically asymptomatic except for a weight loss of 8 kg over 6-month period prior to presentation. Patient's spirometry was suggestive of a restrictive pattern and further investigation using a high-resolution computed tomography (HRCT) of the chest showed bilateral diffuse ground-glass reticulonodular opacities with subpleural sparing suggestive of interstitial pneumonitis. A bronchoscopy with bronchoalveolar lavage revealed organisms consistent with Pneumocystis jirovecii on gomori-methenamine-silver (GMS) staining. Beta-d-glucan testing in serum revealed a level of >500 pg/mL (normal 0-59 pg/mL) further supportive of Pneumocystis jirovecii infection. Patient was treated with a 6-week course of trimethoprim-sulfamethoxazole. His weight loss and beta-d-glucan levels improved over a course of 6 months, and he continues to be on trimethoprim-sulfamethoxazole prophylaxis. CONCLUSION: Late-onset Pneumocystis jirovecii infection in kidney transplant recipients can have an atypical presentation. Treating physicians should consider PJP in the differential diagnosis of unexplained weight loss in pediatric kidney transplant recipients, especially those receiving a large cumulative burden of immunosuppression.

Neuroendocrine Cell Hyperplasia of Infancy. Clinical Score and Comorbidities.

Rationale: Neuroendocrine cell hyperplasia of infancy (NEHI) is an important form of children's interstitial and diffuse lung disease for which the diagnostic strategy has evolved. The prevalence of comorbidities in NEHI that may influence treatment has not been previously assessed.Objectives: To evaluate a previously unpublished NEHI clinical score for assistance in diagnosis of NEHI and to assess comorbidities in NEHI.Methods: We performed a retrospective chart review of 199 deidentified patients with NEHI from 11 centers. Data were collected in a centralized Research Electronic Data Capture registry and we performed descriptive statistics.Results: The majority of patients with NEHI were male (66%). The sensitivity of the NEHI Clinical Score was 87% (95% confidence interval [CI], 0.82-0.91) for all patients from included centers and 93% (95% CI, 0.86-0.97) for those with complete scores (e.g., no missing data). Findings were similar when we limited the population to the 75 patients diagnosed by lung biopsy (87%; 95% CI, 0.77-0.93). Of those patients evaluated for comorbidities, 51% had gastroesophageal reflux, 35% had aspiration or were at risk for aspiration, and 17% had evidence of immune system abnormalities.Conclusions: The NEHI Clinical Score is a sensitive tool for clinically evaluating NEHI; however, its specificity has not yet been addressed. Clinicians should consider evaluating patients with NEHI for comorbidities, including gastroesophageal reflux, aspiration, and immune system abnormalities, because these can contribute to the child's clinical picture and may influence clinical course and treatment.

Ceftolozane/Tazobactam Treatment of Multidrug-resistant Pseudomonas aeruginosa Infections in Children.

The clinical use, safety and effectiveness of ceftolozane/tazobactam among 13 patients 3 months to 19 years of age infected with multidrug-resistant Pseudomonas aeruginosa are described. All but one patient achieved clinical cure after initial treatment. Adverse drug events attributed to treatment included transaminitis and neutropenia which occurred in 2 patients and resolved upon dose reduction.

Pulmonary Function Testing in Pediatric Pneumonia Patients With Wheezing Younger Than 3 Years of Age.

Background. Wheezing symptoms are one of the risk factors in young pneumonia patients that often leads to asthma development. Infant pulmonary function test (iPFT) is potentially a useful tool to help identify and manage these high-risk pneumonia patients. Methods. To examine whether patients with wheezing symptoms are more likely to have poorer pulmonary function and treatment outcomes, and also to explore the clinical benefit of iPFT in young pneumonia patients, we conducted a retrospective analysis of 1005 pneumonia inpatients <3 years of age who had undergone iPFT testing in 2016 at Liuzhou Maternity and Child Healthcare Hospital in Guang-Xi, China. Results. We identified from the hospital database 505 pneumonia patients who presented with wheezing and 500 without wheezing. Univariate analysis showed that wheezing symptoms, viral infection, age <1 year, female gender, and prematurity were significantly associated with poorer iPFT results. After adjusting for confounders, patients with wheezing showed significantly poorer pulmonary function. Patients with wheezing had longer length of stay (7.9 ± 3.9 days vs 6.5 ± 2.6 days; P < .001) and lower percent with no residual clinical symptoms at discharge (58% vs 98%; P < .001) when compared with those of non-wheezing patients. In addition, 81% of patients with viral infection as compared with 43% of patients with nonviral infection presented with wheezing symptoms (P < .001). Conclusion. Wheezing symptoms were associated with poorer iPFT measures and treatment outcomes for pneumonia inpatients <3 years of age. Patients with wheezing had poorer treatment outcomes. iPFT can be useful in assessing and monitoring young patients with high risk of developing asthma or chronic lung disease later in life.

Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Pulmonary Exacerbation in a Pediatric Cystic Fibrosis Patient.

Ceftaroline, an advanced generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA), may present a new therapeutic alternative for treating lung infections among patients with cystic fibrosis. We report a case of ceftaroline therapy in a pediatric patient with cystic fibrosis, whose dose was increased from 9.7 mg/kg/dose every 12 hours to 10.8 mg/kg/dose every 8 hours by using pharmacokinetic analyses.

Airway obstruction is increased in pneumocystis-colonized human immunodeficiency virus-infected outpatients.

We investigated the relationship of Pneumocystis colonization, matrix metalloprotease levels in sputum, and airway obstruction in a cohort of human immunodeficiency virus (HIV)-infected outpatients. Pneumocystis-colonized subjects had worse obstruction of airways and higher levels of matrix metalloprotease-12 in sputa, suggesting that Pneumocystis colonization may be important in HIV-associated chronic obstructive pulmonary disease.