Michael Tracy, MD

Abstract

Background: There is increasing interest in the pulmonary microbiome's bacterial and viral communities, particularly in the context of chronic airway infections in cystic fibrosis (CF). However, the isolation of microbial DNA from the sputum from patients with CF is technically challenging and the optimal protocols for the analysis of viral species, including bacteriophage, from clinical samples remains difficult. Materials and Methods: In this study, we evaluate a set of methods developed for processing and analyzing sputum from patients with CF with the goal of detecting Pf bacteriophage virion-derived nucleic acid. We evaluate the impact of bead beating, deoxyribonuclease digestion, and heating steps in these protocols focusing on the quantitative assessment of Pseudomonas aeruginosa and Pf bacteriophage in sputum. Results: Based on these comparative data, we describe an optimized protocol for processing sputum from patients with CF and isolating DNA for polymerase chain reaction or sequencing-based studies. Conclusion: These studies demonstrate the assessment of a specific bacteriophage and bacteria in sputum from patients with CF.

View details for DOI 10.1089/phage.2020.0003

View details for PubMedID 32626852

View details for PubMedCentralID PMC7327540

View details for Web of Science ID 000466776701222

View details for Web of Science ID 000466776701221

View details for DOI 10.1002/ppul.24126

View details for Web of Science ID 000446457700006

Abstract

Fungal infection in cystic fibrosis (CF) is a recognized challenge, with many areas requiring further investigation. Consensus definitions exist for allergic bronchopulmonary aspergillus in CF, but the full scope of clinically relevant non-allergic fungal disease in CF-asymptomatic colonization, transient or chronic infection localized to endobronchial mucus plugs or airway tissue, and invasive disease-is yet to be clearly defined. Recent advances in mycological culture and non-culture identification have expanded the list of both potential pathogens and community commensals in the lower respiratory tract. Here we aim to outline the current understanding of fungal presence in the CF respiratory tract, risk factors for acquiring fungi, host-pathogen interactions that influence the role of fungi from bystander to pathogen, advances in the diagnostic approaches to isolating and identifying fungi in CF respiratory samples, challenges of classifying clinical phenotypes of CF patients with fungi, and current treatment approaches. Development and validation of biomarkers characteristic of different fungal clinical phenotypes, and controlled trials of antifungal agents in well-characterized target populations, remain central challenges to surmount and goals to be achieved.

View details for PubMedID 29992775

Abstract

This review aims to provide clinicians engaged in the care of infants and children an update on the current understanding of the epidemiology, etiology, diagnostic evaluation, and clinical management of complicated pneumonia. The review provides timely information surrounding areas of consensus and ongoing research.The epidemiology and etiologies of complicated pneumonia continue to evolve over the past several decades in context of the introduction of new vaccines. We review uncommon and emerging pathogens. Immunocompromised patients are particularly at risk for complications. The 2011 clinical practice guidelines for pediatric community-acquired pneumonia from The Pediatric Infectious Diseases Society/Infectious Diseases Society of America and the British Thoracic Society are changing approaches to evaluation and management. The efficacy of new diagnostic laboratory studies, and imaging techniques, continues to be studied. Antibiotics are the mainstay of treatment, with several new options to consider. Techniques for the drainage of parapneumonic effusions continue to optimize.Although much is known about complicated pneumonia, it remains a significant burden. New diagnostic and therapeutic interventions hold much promise. This review seeks to provide clinicians with evidence that motivates a reasoned approach to the evaluation and management of complicated pneumonia.

View details for PubMedID 29528891

View details for Web of Science ID 000449980302106

Abstract

Bronchopulmonary dysplasia (BPD) or chronic lung disease of infancy BPD was originally described 50 years ago, in 1967 by Northway et al. This article possesses two fundamental objectives to provide: a brief historical perspective on BPD; and an update relative to current notions of epidemiology, pathophysiology, evaluation, and clinical management of BPD complicated by vascular disease. The review highlights areas of consensus and ongoing uncertainty.The clinical cause and presentation of infants with BPD has evolved over the past several decades. Considerable improvements in neonatal care, including surfactant replacement therapies, antenatal steroids, nutritional support, ventilator management, and attention to the potential of oxygen toxicity, underlie the evolution of BPD. Most children with BPD improve over time. However, in the presence of vascular disease, the morbidity and mortality associated with BPD increases considerably. Though recent recommendations include procuring an echocardiogram to screen for pulmonary hypertension in infants with established BPD, there is less agreement surrounding the additional diagnostic and putative treatment modalities for infants with BPD and pulmonary hypertension. The indications, rationale, potential benefits, and risks of vasodilator therapy in BPD are discussed.The pediatric community has 50 years of experience with BPD. Past experience should be used to inform present and future diagnostic and treatment strategies. This review seeks to arm the clinician with evidence that motivates a physiology-based approach to the management of infants with BPD and pulmonary hypertension.

View details for DOI 10.1097/MOP.0000000000000490

View details for Web of Science ID 000401074000011

View details for PubMedID 28338487

Abstract

Children with Tetralogy of Fallot, Pulmonary Atresia, and Major Aortopulmonary Collaterals (TOF/PA/MAPCAs) undergoing unifocalization surgery are at risk for developing more postoperative respiratory complications than children undergoing other types of congenital heart surgery. Bronchoscopy is used in the perioperative period for diagnostic and therapeutic purposes. In this study, we describe bronchoscopic findings and identify factors associated with selection for bronchoscopy.Retrospective case-control.All patients with TOF/PA/MAPCAs who underwent unifocalization surgery from September 2005 through March 2016 were included. Patients who underwent bronchoscopy in the perioperative period were compared to a randomly selected cohort of 172 control patients who underwent unifocalization without bronchoscopy during the study period.Forty-three children underwent perioperative bronchoscopy at a median of 9 days postoperatively. Baseline demographics were similar in bronchoscopy patients and controls. Patients who underwent bronchoscopy were more likely to have a chromosome 22q11 deletion and were more likely have undergone unifocalization surgery without intracardiac repair. These patients had a longer duration of mechanical ventilation, ICU duration, and length of hospitalization. Abnormalities were detected on bronchoscopy in 35 patients (81%), and 20 (35%) of bronchoscopy patients underwent a postoperative intervention related to abnormalities identified on bronchoscopy.Bronchoscopy is a useful therapeutic and diagnostic instrument for children undergoing unifocalization surgery, capable of identifying abnormalities leading to an additional intervention in over one third of patients. Special attention should be given to children with a 22q11 deletion to expedite diagnosis and intervention for possible airway complications.

View details for DOI 10.1002/ppul.23732

View details for PubMedID 28504356

View details for DOI 10.1542/hpeds.2017-0047

Abstract

Allergic bronchopulmonary aspergillosis (ABPA), a progressive fungal allergic lung disease, is a common complication of asthma or cystic fibrosis. Although ABPA has been recognized since the 1950s, recent research has underscored the importance of Th2 immune deviation and granulocyte activation in its pathogenesis. There is also strong evidence of widespread under-diagnosis due to the complexity and lack of standardization of diagnostic criteria. Treatment has long focused on downregulation of the inflammatory response with prolonged courses of oral glucocorticosteroids, but more recently concerns with steroid toxicity and availability of new treatment modalities has led to trials of oral azoles, inhaled amphotericin, pulse intravenous steroids, and subcutaneously-injected anti-IgE monoclonal antibody omalizumab, all of which show evidence of efficacy and reduced toxicity.

View details for PubMedID 29376934

View details for Web of Science ID 000390749607182

View details for DOI 10.3390/jof2020017

View details for Web of Science ID 000390749606226

View details for Web of Science ID 000390749600791

Abstract

Many pediatric lung diseases are characterized by infection. These infections are generally diagnosed, studied, and treated using standard culture methods to identify 'traditional pathogens'. Based on these techniques, healthy lungs have generally been thought to be sterile. However, recent advances in culture-independent microbiological techniques challenged this paradigm by identifying diverse microbes in respiratory specimens (respiratory microbiomes) from both healthy people and those with diverse lung diseases. In addition, growing evidence suggests a link between gastrointestinal microbiomes and inflammatory diseases of various mucosal surfaces, including airways.This article reviews the rapidly developing field of respiratory microbiome research, emphasizing recent progress made employing increasingly sophisticated technologies. Although many of the relevant studies have focused on adults with cystic fibrosis, recent research has included children and adults with other respiratory diseases, as well as healthy individuals. These studies suggest that even healthy children have airway microbiomes, and that both respiratory and gastrointestinal microbiomes often differ between healthy people and those with different types and severities of airway disease. The causal relationships between microbiomes, disease type and progression, and treatments such as antibiotics must now be defined.The advent of culture-independent microbiological techniques has transformed how we think about the relationship between microbes and airway disease. More research is required to translate these findings to improved therapies and preventive strategies.

View details for DOI 10.1097/MOP.0000000000000212

View details for Web of Science ID 000354214800014

View details for PubMedID 25888147

View details for PubMedCentralID PMC4443818

View details for Web of Science ID 000377582808179