Constrictive bronchiolitis in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

BACKGROUND: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterised by multifocal proliferation of neuroendocrine cells and belongs in the spectrum of pulmonary neuroendocrine tumours. Some patients with DIPNECH develop airflow obstruction but the relationship between the two entities remains unclear. METHODS: We performed a computer-assisted search of the Mayo Clinic's electronic medical records for biopsy-proven cases of DIPNECH. We extracted clinical, pulmonary function, imaging and histopathological data along with treatments and outcomes. RESULTS: Among 44 patients with DIPNECH 91% were female and the median age was 65 years (interquartile range 56-69 years); 73% were never-smokers. Overall, 38 patients (86%) had respiratory symptoms including cough (68%) and dyspnoea (30%); 45% were previously diagnosed to have asthma or COPD. Pulmonary function testing showed an obstructive pattern in 52%, restrictive pattern in 11%, mixed pattern in 9%, nonspecific pattern in 23%, and was normal in 5%. On chest computed tomography scan, 95% manifested diffuse nodules and 77% manifested mosaic attenuation. For management, 25% of patients were observed without pharmacological therapy, 55% received an inhaled bronchodilator, 41% received an inhaled corticosteroid, 32% received octreotide; systemic steroids, azithromycin, or combination chemotherapy was employed in four patients (9%). Of 24 patients with available follow-up pulmonary function tests, 50% remained stable, 33% worsened and 17% improved over a median interval of 21.3 months (interquartile range 9.7-46.9 months). CONCLUSION: DIPNECH occurs mostly in women and manifests diffuse pulmonary nodules and mosaic attenuation on imaging. It is commonly associated with airflow obstruction due to constrictive bronchiolitis, which manifests limited response to current pharmacological therapy.

Recent advances in the understanding of bronchiolitis in adults.

Bronchiolitis is injury to the bronchioles (small airways with a diameter of 2 mm or less) resulting in inflammation and/or fibrosis. Bronchioles can be involved in pathologic processes that involve predominantly the lung parenchyma or large airways, but, in some diseases, bronchioles are the main site of injury ("primary bronchiolitis"). Acute bronchiolitis caused by viruses is responsible for most cases of bronchiolitis in infants and children. In adults, however, there is a wide spectrum of bronchiolar disorders and most are chronic. Many forms of bronchiolitis have been described in the literature, and the terminology in this regard remains confusing. In clinical practice, a classification scheme based on the underlying histopathologic pattern (correlates with presenting radiologic abnormalities) facilitates the recognition of bronchiolitis and the search for the inciting cause of the lung injury. Respiratory bronchiolitis is the most common form of bronchiolitis in adults and is usually related to cigarette smoking. Currently, the diagnosis of respiratory bronchiolitis is generally achieved based on the clinical context (smoking history) and chest CT findings. Constrictive (obliterative) bronchiolitis is associated with airflow obstruction and is seen in various clinical contexts including environmental/occupational inhalation exposures, transplant recipients (bronchiolitis obliterans syndrome), and many others. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is increasingly recognized and can be associated with progressive airflow obstruction related to constrictive bronchiolitis ("DIPNECH syndrome"). Diffuse aspiration bronchiolitis is a form of aspiration-related lung disease that is often unsuspected and confused for interstitial lung disease. Novel forms of bronchiolitis have been described, including lymphocytic bronchiolitis and alveolar ductitis with emphysema recently described in employees at a manufacturing facility for industrial machines. Bronchiolitis is also a component of vaping-related lung injury encountered in the recent outbreak.

Impact of Nasopharyngeal FilmArray Respiratory Panel Results on Antimicrobial Decisions in Hospitalized Patients.

Objective: To determine whether results of the nasopharyngeal FilmArray respiratory panel (NP-FARP) influenced antibiotic decisions. Methods: We reviewed the medical records of nonintensive care unit (ICU) inpatients that had an NP-FARP performed at our institution between June 2013 and June 2014. The inpatient records were reviewed 48 hours after the NP-FARP for the following data: demographic information; NP-FARP, serum procalcitonin, and methicillin-resistant Staphylococcus aureus nasal swab (MRSA NS) results; antibiotics prior and post-48 hours of the NP-FARP result; and the current immunosuppression status. Clinical outcome data were not obtained. Patients were categorized into those who had a positive (+) or a negative (-) NP-FARP. We further subdivided these two categories into groups A, B, and C based on the antibiotic modifications 48 hours after their NP-FARP result. Group A included patients who were never initiated on antimicrobial therapy. Patients whose antibiotics were discontinued or deescalated were placed in group B. Patients with antibiotic escalation or continuation without change constituted group C. We compared and analyzed groups A, B, and C in the (+) and (-) NP-FARP cohorts. Results: A total of 545 patients were included. There were 143 (26%) patients with positive and 402 (74%) patients with negative NP-FARPs. Comparison of groups A, B, and C between those with a (+) and (-) NP-FARP were as follows: (+) A and (-) A, 28/143 (20%) and 84/402 (21%); (+) B and (-) B, 59/143 (41%) and 147/402 (37%); and (+) C and (-) C, 56/143 (39%) and 171/402 (43%), respectively. We found no statistically significant differences between groups (+) A versus (-) A, (+) B versus (-) B, and (+) C versus (-) C with respect to age, gender, MRSA NS result, procalcitonin result, or concurrent immunosuppression. Conclusion: In non-ICU inpatients, NP-FARP alone or in combination with procalcitonin or MRSA NS did not influence antibiotic decisions during the study period.

Comparison of Respiratory Pathogen Detection in Upper versus Lower Respiratory Tract Samples Using the BioFire FilmArray Respiratory Panel in the Immunocompromised Host.

Background: The FilmArray Respiratory Panel (FARP) (BioFire Diagnostics, Inc.) is a multiplex, polymerase chain reaction (PCR) technique that can detect 17 respiratory viruses and 3 bacterial targets in a single reaction. Immunocompromised hosts (ICH) with respiratory illnesses often undergo bronchoscopy with bronchoalveolar lavage (BAL). This prospective study aimed to evaluate the yield and concordance of NP and BAL FARP testing when performed on the same patient concurrently. Methods: From February to December 2016, 125 patients (100 ICH and 25 non-ICH) were enrolled. NP swabs and BAL samples were sent for FARP testing. Results: The yield of the BAL FARP among ICH and non-ICH was 24% (24/100) and 8% (2/25), respectively. The yield of positive NP swabs in ICH was 27% (27/100) versus 4% (1/25) in non-ICH. The majority of patients (89%; 111/125) had concordant results between NP and BAL specimens. Of the 24 ICH patients who had a positive BAL FARP, the majority (79%) had the same pathogen detected from the NP swab. Conclusion: The FARP may be useful in the ICH. Given the high concordance, in patients whom a pathogen is identified on the NP FARP, a FARP performed on BAL will likely yield the same result. However, if the NP FARP is negative, performing the test on a BAL sample may have an incremental yield.

Treatment of acute exacerbations of interstitial lung disease.

INTRODUCTION: Interstitial lung diseases (ILD) include a broad range of diffuse parenchymal lung disorders of known and unknown etiologies. Patients with ILD can experience acute exacerbations (AE) which are associated with extremely high morbidity and mortality. Little is known about the etiology of AEs, and whether inciting triggers (such as infection) result in an aberrant inflammatory response in a predisposed host. Areas covered: The majority of data regarding AE-ILD comes from the idiopathic pulmonary fibrosis (IPF) population and is extrapolated to other forms of ILD. For the purposes of this review we have summarized the current literature regarding AE of IPF, and when available have included data from AE of other ILDs. Expert commentary: Therapeutic options for AE are limited without definitive treatments available, and the prognosis is often poor. Treatment is mainly based on correcting hypoxemia, looking for reversible etiologies of respiratory decline, and palliation of symptoms. Overall little is known about the pathogenesis of ILDs and AE-ILD, more research is needed in hopes of identifying better treatment options.

The Role of Infection in Interstitial Lung Diseases: A Review.

Interstitial lung disease (ILD) comprises an array of heterogeneous parenchymal lung diseases that are associated with a spectrum of pathologic, radiologic, and clinical manifestations. There are ILDs with known causes and those that are idiopathic, making treatment strategies challenging. Prognosis can vary according to the type of ILD, but many exhibit gradual progression with an unpredictable clinical course in individual patients, as seen in idiopathic pulmonary fibrosis and the phenomenon of "acute exacerbation"(AE). Given the often poor prognosis of these patients, the search for a reversible cause of respiratory worsening remains paramount. Infections have been theorized to play a role in ILDs, both in the pathogenesis of ILD and as potential triggers of AE. Research efforts thus far have shown the highest association with viral pathogens; however, fungal and bacterial organisms have also been implicated. This review aims to summarize the current knowledge on the role of infections in the setting of ILD.

Current concepts and dilemmas in idiopathic interstitial pneumonias.

Idiopathic interstitial pneumonias comprise approximately one-third of interstitial lung diseases (also called diffuse parenchymal infiltrative lung diseases). The classification of idiopathic interstitial pneumonias has undergone several revisions since the initial description of 40 years ago, and the most recent version was published in 2013. Although some aspects have been clarified, this group of heterogeneous disorders continues to be a source of confusion and misunderstanding in clinical applications. In this article, we explore several topical themes in the evaluation and management of patients with idiopathic interstitial pneumonias.

Erdheim Chester Disease treated successfully with cladribine.

A 61-year-old previously healthy male with a history of progressive fatigue, lower extremity edema, and dyspnea for 4 months was hospitalized with pericardial and pleural effusions (Figure 1A, B). Lung, pleural, and pericardial biopsies were consistent with Erdheim-Chester disease. He was treated with systemic steroids, and ultimately tried on PEG-interferon. He deteriorated clinically and the disease progressed to include CNS manifestations. Ultimately he was treated with Cladribine, at a dose 0.014 mg/kg on day 1, followed by 0.09 mg/kg/day = 6.4 mg IV for 6 additional days. He received 2 further cycles of 0.14 mg kg/day for 7 days (1 month apart). After 3 cycles he improved significantly both clinically and radiographically. Six months post-treatment objective testing showed improvement in cardiac, neurologic, and pulmonary disease. Erdheim Chester Disease (ECD) is a rare non Langerhans cell histiocytosis. Only several hundred cases have been reported in the literature. Treatment for ECD is reserved for those with symptomatic disease, asymptomatic CNS involvement, or evidence of organ dysfunction. There is no standard treatment regimen: Current options include corticosteroids, Interferon alpha (IFN), systemic chemotherapy, and radiation therapy. The occurrence of the V600EBRAF mutation in about 50% of patients can make these patients amenable to targeted therapy with BRAF kinase inhibitors (e.g. Vemurafenib). More recently the presence of N/KRAS, and PIK3CA mutations have provided further rational for targeted therapies. The cytokine profile in patients with ECD suggests monocyte activation cladribine, a purine analogue toxic to monocytes, has also been studied as a treatment for ECD, especially in patients who test negative for the BRAF mutation.

Introducing routine HIV screening for patients on an internal medicine residency inpatient service: a quality improvement project.

The US Centers for Disease Control and Prevention (CDC) recommend human immunodeficiency virus (HIV) screening for all persons aged 13 to 64 years who present to a health care provider. We sought to improve adherence to the CDC guidelines on the Internal Medicine Resident Hospital Service. We surveyed residents about the CDC guidelines, sent email reminders, provided education, and engaged them in friendly competition. Credit for guideline adherence was awarded if an offer of HIV screening was documented at admission, if a screening test was performed, or if a notation in the resident sign out sheet indicated why screening was not performed. We examined HIV screening of a postintervention group of patients admitted between August 8, 2012, and June 30, 2013, and compared them to a preintervention group admitted between August 1, 2011, and June 30, 2012. Postintervention offers of HIV screening increased significantly (7.9% [44/559] vs 55.5% [300/541]; P<.001), as did documentation of residents' contemplation of screening (8.9% [50/559] vs 67.5% [365/541]; P<.001). A significantly higher proportion of HIV screening tests was ordered postintervention (7.7% [43/559] vs 44.4% [240/541]; P<.001). Monthly HIV screening documentation ranged from 0% (0/53) to 17% (9/53) preintervention, whereas it ranged from 30.6% (11/36) to 100% (62/62) postintervention. HIV screening adherence can be improved through resident education, friendly competition, and system reminders. Barriers to achieving sustained adherence to the CDC guidelines include a heterogeneous patient population and provider discomfort with the subject.

Wheezes and desert breezes: when asthma and valley fever collide.

OBJECTIVE: To evaluate interactive effects of pulmonary coccidioidomycosis and asthma. METHODS: We identified three groups of 33 age- and sex-matched patients: Group 1 (both asthma and coccidioidomycosis), Group 2 (asthma only), and Group 3 (pulmonary coccidioidomycosis only). Predetermined end points included: rate of disseminated coccidioidomycosis, duration of symptoms and antifungal therapy, hospitalization, death, and escalation of asthma therapies. RESULTS: Baseline characteristics were similar across groups. Group 1 patients had worsening asthma outcomes (except forced expiratory volume in 1 s) with coccidioidomycosis. They required more asthma medications (median, 2.0 vs 0.0; p < 0.001), more corticosteroids (mean [SD], 0.9 [4.2] vs 0.3 [0.6]; p < 0.001), and more healthcare visits (mean [SD], 0.2 [0.4] vs 0.1 [0.3]; p = 0.03). Groups 1 and 3 had no differences in coccidioidal end points, including rates of dissemination (1 vs 0; p > 0.99), symptom duration (mean, 15.2 vs 23.6 weeks; p = 0.24), antifungal treatment (n = 21 [63.6%] vs n = 24 [72.7%]; p = 0.60), and treatment duration (median, 26.5 vs 11 weeks; p = 0.09). Ten patients in Group 1 versus none in Group 3 required systemic corticosteroids for coccidioidomycosis (p < 0.001). CONCLUSIONS: Active pulmonary coccidioidomycosis significantly worsens asthma outcomes. Asthma (or its treatment) does not worsen coccidioidal outcomes, despite increasing the likelihood of treatment with systemic corticosteroids.

FilmArray Respiratory Panel Assay: Comparison of Nasopharyngeal Swabs and Bronchoalveolar Lavage Samples.

The FilmArray respiratory panel (FARP) reliably and rapidly identifies 17 viruses and 3 bacterial pathogens. A nasopharyngeal swab FARP (NP FARP) is performed for many patients with respiratory symptoms. For patients who are acutely ill or immunocompromised or fail to improve, a bronchoalveolar lavage sample FARP (BAL FARP) is performed in addition to the NP FARP. To date, no studies have compared the yield of a BAL FARP with that of an NP FARP. We retrospectively studied all patients who had a BAL FARP within 7 days after an NP FARP between June 2013 and May 2014. Demographic information, comorbidities, FARP results, and all microbiologic data from BAL fluid were collected. Eighty-six patients had a BAL FARP performed within 7 days (mean, 1.6; median, 1) after an NP FARP. Of these, 66 (77%) had concordant BAL and NP FARP results: 15 (23%) had the same pathogen identified from the NP and BAL FARPs, and 51 (77%) had concordant negative FARP results. In 18 of the 86 patients (21%), a pathogen was detected from the NP FARP; of these, 15 (83%) had a concordant match on a subsequent BAL FARP, and the remaining 3 had negative BAL FARPs. In 17 of the 86 patients (20%), pathogens were identified from the BAL FARPs that were not detected by the NP FARPs; of these, 16 (94%) had initial negative NP FARPs. The data suggest that once a pathogen is identified by an NP FARP, a subsequent BAL FARP is unlikely to add new microbiologic information. However, a BAL FARP may provide new, useful microbiologic information when performed within 7 days after a negative NP FARP.

The impact of early and brief corticosteroids on the clinical course of primary pulmonary coccidioidomycosis.

OBJECTIVE: Primary pulmonary coccidioidomycosis can often be associated with hypersensitivity symptoms treatable with a short course of palliative corticosteroids. Long-term use of corticosteroids is a known risk factor for severe or disseminated infection but the effects of short-term use are not known. METHODS: A retrospective review was conducted of immunocompetent patients with acute pulmonary coccidioidomycosis who received systemic corticosteroids for relief of coccidioidal-related symptoms. Age- and sex-matched controls were also reviewed. Predetermined end-points were assessed. RESULTS: Seventy-four patients met inclusion criteria for the corticosteroid-treated group, and 74 controls were identified. Cumulative corticosteroid (prednisone-equivalent) doses were 10 mg → 3,600 mg (mean = 206 mg; median = 120 mg). Corticosteroids were prescribed most commonly for rash 43/74 [58%] or asthma/wheezing/cough 30/74 [41%]. Coccidioidal-related hospitalization occurred in 19 patients in the corticosteroid group vs. 22 in the control group (P = .58). Coccidioidal-related symptoms resolved within a mean of 19 weeks (median = 8 weeks [range = 2-208 weeks]) vs. 32.3 weeks (median = 8 weeks [range = 1-1040 weeks]) in the corticosteroid and control groups (P = .38). Relapse of symptoms occurred in 12% of both groups (P > .99). Extrapulmonary dissemination occurred in 3% vs. 4.0% (P > .99) in the corticosteroid and control groups, respectively. CONCLUSION: This study found no adverse effects of short-term corticosteroid therapy for early symptomatic treatment in acute pulmonary coccidioidomycosis.