Faculty Bibliography

BACKGROUND/UNASSIGNED:Exacerbations of noncystic fibrosis bronchiectasis (bronchiectasis) are associated with reduced health-related quality of life and increased mortality, likelihood of hospitalisation and lung function decline. This study investigated patient clinical characteristics associated with exacerbation frequency. METHODS/UNASSIGNED:A cross-sectional cohort study of patients ≥18 years with bronchiectasis enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR) September 2008-March 2020. Patients were stratified by exacerbation frequency in their 2 years before enrolment. Patient demographics, respiratory symptoms, healthcare resource utilisation, microbiology, modified bronchiectasis severity index (mBSI) and select comorbidities were collected at enrolment. Patient characteristics associated with exacerbation frequency were assessed using a negative binomial model. RESULTS/UNASSIGNED:% predicted, asthma, and gastro-oesophageal reflux disease were associated with more exacerbations. CONCLUSIONS/UNASSIGNED:infection in patients with bronchiectasis and multiple exacerbations.

BACKGROUND:associated with exacerbation frequency (objective 2). METHODS:% predicted over 24 months stratified by baseline exacerbation frequency. RESULTS:% predicted was significantly lower at baseline (P < 0.0001) and at 12 (P = 0.0002) and 24 month follow-ups (P < 0.0001). CONCLUSIONS:decline may not differ by baseline exacerbation frequency.

RATIONALE/BACKGROUND:Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM) pulmonary disease. OBJECTIVES/OBJECTIVE:To describe the epidemiology, patient management, and treatment outcomes of NTM infections in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR). METHODS:This was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008-2019. The study included patients with ≥1 positive NTM respiratory culture in the 24-month baseline period (baseline NTM cohort) and/or during the annual follow-up visits (incident NTM cohort). Incidence, prevalence, baseline patient characteristics, treatment exposure, treatment outcomes, and respiratory clinical outcomes were described in the baseline NTM cohort, incident NTM cohort, and both cohorts combined (prevalent NTM cohort). RESULTS:Between 2008 and 2019, 37.9% (1457/3840) of patients with bronchiectasis in the US BRR met the inclusion criteria for this study and were reported to have Mycobacterium avium complex (MAC) and/or Mycobacterium abscessus complex (MABSC) infections. MAC prevalence increased steadily in the US BRR during 2009-2019; incidence was relatively stable, except for a peak in 2011 followed by a slow decrease. MABSC and mixed MAC/MABSC infections were rare. Most patients with bronchiectasis and NTM infections in the registry were female, White, and aged >65 years. The antibiotics administered most commonly reflected current guidelines. In the prevalent cohort, 44.9% of MAC infections and 37.1% of MABSC infections remained untreated during follow-up, and MAC treatment was initiated with delay (>90 days after positive NTM respiratory culture) twice as frequently as promptly (≤90 days after positive NTM respiratory culture) (68.6% vs 31.4%, respectively). The median time from diagnosis to treatment was shorter for MABSC versus MAC infections (194.0 days [interquartile range (IQR) 8.0, 380.0] vs 296.0 days [IQR 35.0, 705.0], respectively). Among patients with MAC infections who completed treatment, 27.6% were classified as cured and 29.6% as treatment failure during the annual follow-up visit window. For MABSC, these proportions were 25.0% and 28.0%, respectively. CONCLUSIONS:A considerable proportion of MAC and MABSC infections were untreated or treated after initial delay/observation. MABSC infections were more likely to be treated and start treatment sooner than MAC infections. Further longitudinal studies are warranted to evaluate the monitor-with-delay approach and inform clinical guidelines.

Airway clearance is a critical component of both maintenance of respiratory health and management of acute respiratory illnesses. The process of effective airway clearance begins with the recognition of secretions in the airway and culminates in expectoration or swallowing. There are multiple points on this continuum at which neuromuscular disease causes impaired airway clearance. This can result in an otherwise mild upper respiratory illness progressing unabated from an easily managed condition to a severe, life-threatening lower respiratory illness requiring intensive therapy for patient recovery. Even during periods of relative health, airway protective mechanisms can be compromised, and patients may have difficulty managing average quantities of secretions. This review summarizes airway clearance physiology and pathophysiology, mechanical and pharmacologic treatment modalities, and provides a practical approach for managing secretions in patients with neuromuscular disease. Neuromuscular disease is an umbrella term used to describe disorders that involve dysfunction of peripheral nerves, the neuromuscular junction, or skeletal muscle. Although this paper specifically reviews airway clearance pertaining to those with neuromuscular diseases (e.g., muscular dystrophy, spinal muscular atrophy, myasthenia gravis), most of its content is relevant to the management of patients with central nervous system disorders such as chronic static encephalopathy caused by trauma, metabolic or genetic abnormalities, congenital infection, or neonatal hypoxic-ischemic injury.

Cystic fibrosis (CF) is an autosomal recessive disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With the advent of highly effective modulator therapy targeting the abnormal CFTR protein, people with CF (PwCF) are living more than 40 years longer than the pre-modulator therapy era. As a result, PwCF are facing new challenges of managing similar comorbidities affecting the average aging population. While CF is notoriously identified as a chronic respiratory disease, the multisystem presence of the CFTR gene can contribute to other organ-related complications acutely, but also heighten the likelihood of chronic conditions not routinely encountered in this cohort. In this overview, we will focus on risk factors and epidemiology for PwCF as they relate to cardiovascular disease, dyslipidemia, CF-related diabetes, pulmonary hypertension, obstructive sleep apnea, CF-liver disease, bone health and malignancy. With increased awareness of diseases affecting a newly aging CF population, a focus on primary and secondary prevention will be imperative to implementing a comprehensive care plan to improve long-term morbidity and mortality.

INTRODUCTION:Little information is available about Stenotrophomonas maltophilia in patients with bronchiectasis. We analyzed data from the US Bronchiectasis and NTM Research Registry to determine its prevalence and association with patient characteristics and severity of disease. METHODS:Baseline and follow-up data were entered into a central web-based database. Patients were grouped into four cohorts based on their baseline cultures: 1) S. maltophilia, no Pseudomonas aeruginsosa, 2) P. aeruginosa, no S. maltophilia, 3) No pathogens, 4) Pathogens other than P. aeruginosa and S. maltophilia. The association between S. maltophilia, demographic characteristics, pulmonary function, exacerbations and hospitalizations was assessed at baseline and one year follow-up. RESULTS:Among 2659 patients, 134 (5.0%) had grown S. maltophilia at baseline. The prior exacerbation rate at baseline was similar in patients with S. maltophilia and P. aeruginosa, but significantly higher than the other two groups. Hospitalizations were more frequent in patients with S. maltophilia or P. aeruginosa. Pre-bronchodilator FEV1 among S. maltophilia patients was between that of Pseudomonas patients and patients without either organism, but was not significantly different from any of the other groups. For all risk-adjusted one-year outcomes, patients with S. maltophilia had a non-significant trend towards worse outcomes compared to patients without P. aeruginosa, but were more similar to patients with P aeruginosa. DISCUSSION:Bronchiectasis patients with S. maltophilia may have worse outcomes than patients without this organism or without P. aeruginosa; further study is needed to determine if the non-significant trends we note are clinically significant.

Non-tuberculous mycobacterial lung disease (NTM-LD) is increasingly recognized as an important cause of chronic respiratory infections. Diagnosing NTM infection in patients with a history of cancer can be delayed, or overlooked, due to potential overlapping symptomatology and similarities among radiographic features, including lung masses, cavities, and nodules. This retrospective case series aims to demonstrate the variable association of NTM-LD and aerodigestive cancers and how in some cases the diagnosis of NTM-LD can be delayed in patients with malignancy. Six patients with biopsy proven aerodigestive malignancy (either lung or head & neck cancer) and culture positive NTM infection were identified through a retrospective review of medical records between 1/1/2013 and 9/20/2020. Their demographic characteristics and clinical course are described to help elucidate both similarities and differences in presentation and diagnosis. Awareness of the association of NTM-LD and lung malignancy may help in early identification of these potential comorbidities and hence influence proactive diagnosis and management.

The typical radiographic presentation for Mycobacterium avium complex lung disease (MAC-LD) is either nodular bronchiectasis or cavitary lung disease. The former is seen most commonly in middle-aged or elderly Caucasian females with the characteristic asthenic phenotype, and the latter in middle-aged male smokers with COPD. We present the case of a young, otherwise healthy woman, with no significant risk factors, who was incidentally found to have MAC-LD with associated bronchiectasis. The patient's treatment and clinical course over a period of 5 years was marred by erratic follow up, intermittent treatment and poor adherence to guideline-based antibiotic therapy. Over this period of time, the patient developed significant worsening of her MAC-LD, macrolide resistance and failure to thrive. Upon presentation 5 years after her initial diagnosis, she had developed MAC-Pleural Disease with an empyema and broncho-pleural fistula. This case illustrates the progression of MAC-LD from nodular bronchiectasis to cavitary disease and pleural involvement leading to clinical deterioration. It highlights challenges related to short and long term management of macrolide resistant MAC-LD and the importance and need for surgical intervention and drainage procedures in patient with MAC-Pleural Disease.

Patients with Mycobacterium avium complex lung disease treated with amikacin liposome inhalation suspension (ALIS) at 2 clinics in the United States were surveyed to assess the frequency and management of ALIS-associated respiratory adverse events. Most respondents experienced these events, but management through physician-guided measures (eg, bronchodilator use, oral rinses, and/or temporary dosing adjustments) resulted in symptomatic improvement.