Douglas K. Hogarth

Electromagnetic navigational bronchoscopy: an effective and safe approach to diagnose peripheral lung lesions unreachable by conventional bronchoscopy in high-risk patients.

Purpose The purpose of this study was to investigate the diagnostic yield and safety of electromagnetic navigation bronchoscopy (ENB) on peripheral lung lesions deemed otherwise unreachable using conventional bronchoscopy in high-risk patients. Methods This was a retrospective chart review involving adults (age, 18 y and older) who underwent ENB for pulmonary lesions located at the fourth order of bronchi or beyond, including subpleural lesions, at the University of Chicago Medical Center. Forty-eight patients underwent ENB by 3 different trained operators from January 2006 to September 2008. There was a short period of inactivity when the device was withdrawn from the market. ENB was reserved for use only in lesions at the fourth order of bronchi or beyond, including subpleural lesions, in patients who are considered high risk for other invasive procedures. Pathologic, cytologic, and microbiologic studies were carried out on recovered samples. Postprocedural chest radiographs were obtained on all patients to detect the presence of procedure-associated complications. Results ENB led to the diagnosis of 37 of 48 (77%) lesions not amenable to conventional bronchoscopic biopsy in high-risk patients. Of the 37 successful procedures, malignancy was identified in 18 patients (49%). Nonsmall cell lung cancer (NSCLC) was diagnosed 16 times, whereas both small cell lung cancer and carcinoid tumor were diagnosed once. In addition, 4 lesions (11%) were found to be infectious, 1 lesion (3%) was found to be granulomatous (noncaseating), and 1 lesion (3%) was diagnosed as organizing pneumonia. Of the 37 successful diagnoses, 13 lesions (35%) were determined to be nonpathologic, benign lesions. Eleven procedures (22%) were unsuccessful in yielding the correct pathologic diagnosis. Nine of the 11 unsuccessful ENB cases (82%) were found to be malignant, 9 of which were identified as NSCLC. Other than NSCLC, 1 neuroendocrine tumor (9%) and 1 metastatic transitional cell carcinoma of the kidney (9%) were identified by alternative, invasive testing methods. The 2 other lesions unsuccessfully diagnosed by ENB were not malignant. One was determined to be infection (histoplasmosis) and the other was diagnosed as an organizing pneumonia. The most common complication noted by all modalities was pneumothorax. ENB carried a pneumothorax rate of 5 of 49 (10%), 2 of which required chest tube insertion for treatment. In the ENB success group, 4 cases (11%) were complicated by pneumothoraces. In the ENB failure group, 1 case (9%) was complicated by a pneumothorax. Conclusions ENB is an effective and low-risk modality for diagnosing pulmonary lesions that are difficult to reach in patients deemed to be at high risk for invasive procedures. Although no clear criteria for the use of ENB currently exist, our study shows that diagnostic sampling can be obtained in 77% of lesions at the fourth order of bronchi or beyond, including subpleural lesions. Clinical Implications ENB is an effective, minimally invasive method for the diagnosis of pulmonary nodules previously deemed unreachable by conventional bronchoscopy in high-risk patients and harbors a low complication rate.

Maternal asthma and microRNA regulation of soluble HLA-G in the airway.

BACKGROUND We previously reported an interaction between maternal asthma and the childs HLA-G genotype on the childs subsequent risk for asthma. The implicated single nucleotide polymorphism at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect might be mediated by these miRs. OBJECTIVE The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies. METHODS We measured soluble HLA-G (sHLA-G) concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR-152 family (miR-148a, miR-148b, and miR-152) transcript levels in airway epithelial cells from the same subjects. RESULTS miR-148b levels were significantly increased in airway epithelial cells from asthmatic subjects with an asthmatic mother compared with those seen in asthmatic subjects without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother but not among those with a nonasthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA). CONCLUSION These combined results are consistent with +3142 allele-specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subjects mother and the subjects genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of the mothers children persist into adulthood.

Isolation of persistent air leaks and placement of intrabronchial valves

OBJECTIVES Alveolar-pleural fistulas causing persistent air leaks are conditions associated with prolonged hospital courses, high morbidity, and possibly increased mortality. Intrabronchial valves serve as a noninvasive therapeutic option for the closure of alveolar-pleural fistulas. METHODS The present review describes a brief history of, and indications for, the placement of intrabronchial valves in patients with persistent air leaks. The essential steps necessary for placement are air leak isolation, airway sizing, and valve deployment. Additionally, the indications and methods for intrabronchial valve removal, along with the potential complications from intrabronchial valve placement, are described. CONCLUSIONS The increased use of intrabronchial valves in the treatment of persistent air leaks requires bronchoscopists and clinicians to understand the procedural steps and techniques necessary for intrabronchial valve placement.

Safety and feasibility of bronchial thermoplasty in asthma patients with very severe fixed airflow obstruction: a case series.

Objective. Bronchial thermoplasty (BT) can provide relief for patients with severe, uncontrolled asthma despite maximal medical therapy. However, it is unclear whether BT is safe in patients with very severe airflow obstruction. Methods. We performed BT in eight patients with severe asthma as defined by Expert Panel Report 3 (EPR-3) guidelines who were poorly controlled despite step 5 therapy. Data were available on each subject for 1 year prior to and 15–72 weeks following BT. Results. The mean (±SEM) pre-bronchodilator forced expiratory volume in one second (FEV1) prior to BT was 51.8 ± 8.6% of predicted, and the mean (±SEM) number of hospitalizations for asthma in the year prior to BT was 2.9 ± 1.2. No subject had an unexpected severe adverse event due to BT. Among the eight patients with follow-up of at least 15 weeks, there was no significant decline in FEV1 (p = .4). Conclusion. We suggest that BT may be safe for asthma patients with severe airflow obstruction and higher hospitalization rates than previously reported.

The prevalence of alpha-1 antitrypsin deficiency among patients found to have airflow obstruction.

Abstract Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic disease that may be manifested by chronic obstructive pulmonary disease. Despite professional society guidelines that recommend broad testing of at-risk individuals, fewer than 10% of affected individuals have been identified. The goals of this study were to estimate the frequency of abnormal AAT genotypes among patients found to have fixed airflow obstruction and to assess the feasibility of having Pulmonary Function Laboratory personnel administer the study. Methods: Nineteen medical centers in the United States participated in the study. Eligible patients (> GOLD II, FEV1/FVC ratio < 0.7, with post-bronchodilator FEV1<80% predicted) were offered testing for AATD by the Pulmonary Function Laboratory personnel at the time of pulmonary function testing. Results: A total of 3,457 patients were tested, of whom 3152 were eligible. Deficient patients (ZZ, SZ) constituted 0.63% of subjects, while 10.88% were carriers (MS, MZ). Neither demographic (except African-American race) nor post-bronchodilator pulmonary function variables (FEV1, FVC, FEV1/FVC ratio, TLC, and FEV1/FVC) allowed us to predict AAT heterozygote or deficiency status. Conclusions: The prevalence of AATD among patients undergoing pulmonary function tests with fixed airflow obstruction was 0.63%. Pulmonary Function Laboratory personnel effectively conducted the study.

Intrabronchial valves: a case series describing a minimally invasive approach to bronchopleural fistulas in medical intensive care unit patients.

Background:Bronchopleural fistulas (BPF) are conditions associated with prolonged hospital course, high morbidity, and possibly increased mortality. The presence of BPFs in critically ill patients may cause difficulty in ventilation and increased oxygen requirements. Intrabronchial valves (Spiration IBV) serve as a noninvasive therapeutic option for the closure of BPFs. Methods:This report is a retrospective description of 3 patients transferred to our medical intensive care unit (ICU) with BPFs and persistent air leaks (PAL). One patient required high levels of oxygen supplementation through a nonrebreather face mask, whereas 2 required mechanical ventilation because of respiratory failure. IBVs were placed in each patient with the intention of closing their BPF and weaning them from respiratory support. Results:The use of IBVs in ICU patients with BPFs and PALs resulted in 1 patient being weaned from the persistent need for a nonrebreather face mask to room air and also aided in the liberation from mechanical ventilation of 2 patients who had been failing spontaneous breathing trials. Conclusions:The use of IBVs is safe and well tolerated in ICU patients with BPFs and PALs. The placement of IBVs results in significant clinical improvement, allowing for either weaning from high levels of oxygen support or liberation from mechanical ventilation.

DNA methylation in lung cells is associated with asthma endotypes and genetic risk

The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults. Asthma status was based on doctors diagnosis and current medication use. Genotyping was performed using various Illumina platforms. Our study revealed a regulatory locus on chromosome 17q12-21 associated with asthma risk and epigenetic signatures of specific asthma endotypes and molecular networks. Overall, these data support a central role for DNA methylation in lung cells, which promotes distinct molecular pathways of asthma pathogenesis and modulates the effects of genetic variation on disease risk and clinical heterogeneity.

Bronchial thermoplasty failure in severe persistent asthma: a case report

Abstract Introduction: Bronchial thermoplasty (BT) is an emerging therapy for patients with severe persistent asthma who remain poorly controlled despite standard maximal medical therapy. Thermoplasty elicits asthma control over time by applying thermal radiofrequency energy to airways to ablate underlying smooth muscle. While this therapy is suggested to eliminate such smooth muscle permanently, no human studies have examined the possibility of treatment failure. Case report: We present a 62-year-old female with severe, refractory asthma symptoms who underwent BT without apparent complications. However, severe symptoms including multiple clinical exacerbations persisted despite BT treatment. Repeat endobronchial biopsy done six months after BT treatment demonstrated persistent smooth muscle hyperplasia in multiple airways that previously had been treated. The patient continued to have uncontrolled, refractory asthma despite multiple therapies. Conclusion: This case is the first to describe a failure of BT to reduce or eliminate airway smooth muscle in a patient with severe persistent asthma. It suggests the potential for treatment failure in the management of these patients after BT and highlights the need for further study of potential BT-refractory patients.

Mediastinal granuloma: a rare cause of dysphagia.

Dysphagia is commonly attributed to disorders arising from dysfunction of the oesophageal mucosa or oesophageal motility. Mediastinal structures causing compression of the oesophagus remain a rare presenting cause of dysphagia. We report a case of a woman presenting with dysphagia to solid foods and associated symptoms of weight loss. Traditional evaluation for dysphagia was unrevealing until cross-sectional imaging suggested a mediastinal obstructive process. The finding of a mediastinal granuloma, distinct from mediastinal fibrosis, as the aetiology of dysphagia is a rare finding, with specific treatment implications. The patient was treated with itraconazole antifungal therapy with an improvement in her symptoms.

A successful bronchial thermoplasty procedure in a “very severe” asthma patient with rare complications: a case report

Abstract Introduction: Bronchial thermoplasty (BT) is a unique bronchoscopic treatment for severe asthma that utilizes radiofrequency ablation to reduce smooth muscle in the bronchial walls. Current studies mainly focused on uncontrolled severe asthma with a forced expiratory volume in 1 second (FEV1) above 60% and associated complications, no human studies have performed on “very severe” asthma as well as its complications. Case study: We present a 60-year-old male with more than 15 years history of very severe asthma, who underwent BT. His FEV1 was only 20.4% predicted, which would have excluded him from all prior clinical trials of BT. The first BT procedure occurred without an issue. After the second BT procedure, he experienced severe dyspnea due to an infection with a non-flu respiratory virus. This illness was complicated by the formation of a pulmonary cyst. During recovering from the third procedure, he developed stomach stones. This is mainly related with taking large amounts of hawthorn previously, also cannot exclude the role of thermal energy injury on gastrointestinal nerve function. Results: Despite these unexpected complications, his quality of life greatly improved after BT, yet his lung function did not improve. Conclusion: This case is the first to describe BT procedures in patient with this level of lung function compromise, although accompanied with rare complications; our report indicates BT may be an opportunity and choice for the “very severe” asthma patients.