Multidisciplinary Approach to Pulmonary Embolism and the Role of the Pulmonary Embolism Response Team.

PURPOSE OF REVIEW: Acute pulmonary embolism (PE) is a leading cause of cardiovascular death and morbidity, and presents a major burden to healthcare systems. The field has seen rapid growth with development of innovative clot reduction technologies, as well as ongoing multicenter trials that may completely revolutionize care of PE patients. However, current paucity of robust clinical trials and guidelines often leave individual physicians managing patients with acute PE in a dilemma. RECENT FINDINGS: The pulmonary embolism response team (PERT) was developed as a platform to rapidly engage multiple specialists to deliver evidence-based, organized and efficient care and help address some of the gaps in knowledge. Several centers investigating outcomes following implementation of PERT have demonstrated shorter hospital and intensive-care unit stays, lower use of inferior vena cava filters, and in some instances improved mortality. Since the advent of PERT, early findings demonstrate promise with improved outcomes after implementation of PERT. Incorporation of artificial intelligence (AI) into PERT has also shown promise with more streamlined care and reducing response times. Further clinical trials are needed to examine the impact of PERT model on care delivery and clinical outcomes.

Acute Respiratory Distress Syndrome in Pregnancy: Updates in Principles and Practice.

Acute respiratory failure occurs in 0.05% to 0.3% of pregnancies and is precipitated by pulmonary and nonpulmonary insults. Acute respiratory distress syndrome (ARDS) is the rapid onset of hypoxemic respiratory failure associated with bilateral pulmonary opacities on chest imaging attributed to noncardiogenic pulmonary edema. The pathophysiological features of ARDS include hypoxemia, diminished lung volumes, and decreased lung compliance. While there is a paucity of data concerning ARDS in the pregnant individual, management principles do not vary significantly between pregnant and nonpregnant patients. The following review will discuss the diagnosis and management of the pregnant patient with ARDS.

Impedance Oscillometry: Emerging Role in the Management of Chronic Respiratory Disease.

PURPOSE OF REVIEW: Chronic respiratory diseases affecting adults and children are widely prevalent, so lung function testing is imperative for diagnosis and management. Spirometry is the traditional standard measure of lung function; however, certain groups of patients are unable to provide accurate and reproducible exhalation maneuvers. Consequently, the impedance oscillometry system (IOS) has been developed as an effort, independent technique to assess airway function in children and the elderly. To better understand this emerging modality, the following review will compare IOS with spirometry, examine the function of the device, provide interpretation strategies, and discuss the evidence supporting its use in adults and children with chronic lung disease. RECENT FINDINGS: In a population of symptomatic adults with suspected COPD, impedance oscillometry resistance measurements correlate with FEV1 and lung resistance increases with the severity of airflow limitation. In patients with asthma, IOS is a sensitive measure of airway hyperresponsiveness and bronchodilator response. Impedance oscillometry is evolving as an alternative measure to assess lung function pediatric and adult populations.

ARDS in pregnancy.

Acute respiratory distress syndrome (ARDS) is an uncommon condition in pregnant patients. The causes of ARDS are associated with obstetric causes such as amniotic fluid embolism, preeclampsia, septic abortion, and retained products of conception or nonobstetric causes that include sepsis, aspiration pneumonitis, influenza pneumonia, blood transfusions, and trauma. An essential component in management of ARDS involves good communication between the obstetrics team and critical care specialist and a fundamental understanding of mechanical ventilatory support. Medical therapies such as nitric oxide and corticosteroids play a complimentary role. Extracorporeal life support is beneficial in the management of the parturient with severe ARDS.

Structured Evaluation and Management of Patients with COPD in an Accredited Program.

Background: Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive condition. Methods: We compared the impact of care received by patients with COPD at Joint Commission-accredited, disease-specific clinics and primary care clinics at an academic health care systemfrom April 2014 to March 2018. Patients with COPD ≥ 40 years old with ≥ 2 outpatient visits 30 days apart were identified. Baseline demographics, disease-specific performance measures, and health care utilization were compared between groups. Propensity matching was conducted and time to the first emergency department (ED) visit and hospitalization was performed using Cox regression analysis. Results: Of 4646 unique patients with COPD, 1114 were treated at disease-specific clinics and 3532 at primary care clinics. The entire group was predominantly female (58.8 %), non-Hispanic White (74.2 %) with a mean age of 65.4 ± 11.4 years consisting of current (47.6 %) or former smokers (38.4 %). In the disease-specific group, performance measures were performed more frequently, and lower rates of ED visits (hazard ratio [HR]=0.31, 95% confidence interval [CI] 0.18-0.54) and hospitalizations (HR 0.41, 95% CI 0.21-0.79) noted in comparison to the primary care group. Conclusions: In this observational study, the implementation of achronic disease management program through accredited disease-specific clinics for patients with COPD was associated with reduced all-cause ED visits and hospitalizations.

Corticosteroids and Outcomes in Solid Organ Transplant Recipients Infected With Severe Acute Respiratory Syndrome Coronavirus 2.

Objective: To examine outcomes in organ transplant and nontransplant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the initial 22 months of the pandemic. Patients and Methods: We used Optum electronic health records to compare outcomes between an adult transplant group and a propensity-matched nontransplant group that tested positive for SARS-CoV-2 from February 1, 2020, to December 15, 2021. Baseline characteristics, hospitalization, intensive care unit admission, mechanical ventilation, renal replacement therapy, inpatient, and 90-day mortality were compared between the transplant and nontransplant groups and among specific transplant recipients. Cox proportional analysis was used to examine hospitalization and mortality by organ transplant, medical therapy, sex, and the period of the pandemic. Results: We identified 876,959 patients with SARS-CoV-2 infection, of whom 3548 were organ transplant recipients. The transplant recipients had a higher risk of hospitalization (30.6% vs 25%, respectively; P<.001), greater use of mechanical ventilation (7.8% vs 5.6%, respectively; P<.001), and increased inpatient mortality (6.7% vs 4.7%, respectively; P<.001) compared with the nontransplant patients. The initiation of mechanical ventilation was significantly more frequent in the transplant group. After adjustment for baseline characteristics and comorbidities, the transplant group had a higher risk of hospitalization (odds ratio, 1.38; 95% confidence interval, 1.19-1.59), without a difference in mortality. In the transplant group, lung transplant recipients had the highest inpatient mortality (11.6%). Conclusion: Among patients with SARS-CoV-2 infection, the transplant recipients were at a higher risk of hospitalization and inpatient mortality; however, mortality was mainly driven by advanced age and comorbidities rather than by transplant status or immunosuppressive medications. Lung transplant recipients had the greatest inpatient and 90-day mortality.

Healthcare Utilization in Patients with Chronic Obstructive Pulmonary Disease Discharged from Coronavirus 2019 Hospitalization.

Rationale: There is concern that patients with chronic obstructive pulmonary disease (COPD) are at greater risk of increased healthcare utilization (HCU) following Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV-2) infection. Objective: To assess whether COPD is an independent risk factor for increased post-discharge HCU. Methods: We conducted a retrospective cohort study of patients with COPD discharged home from a hospitalization due to Coronavirus Disease 2019 (COVID-19) between April 1, 2020, and March 31, 2021, using Optum's de-identified Clinformatics® Data Mart Database (CDM). COVID-19 was identified by an International Classification of Diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis code of U07.1. The primary outcome was HCU (ie, emergency department (ED) visits, readmissions, rehabilitation/skilled nursing facility (SNF) visits, outpatient office visits, and telemedicine visits) nine months post-discharge after COVID-19 hospitalization (from here on "post-discharge") in patients with COPD compared to HCU of patients without COPD. Poisson regression modeling was used to calculate relative risk (RR) and confidence interval (CI) for COPD, adjusted for the other covariates. Results: We identified a cohort of 160,913 patients hospitalized with COVID-19, with 57,756 discharged home and 14,622 (25.3%) diagnosed with COPD. Patients with COPD had a mean age of 75.48 years (±9.49); 55.5% were female and 70.9% were White. Patients with COPD had an increased risk of HCU in the nine months post-discharge after adjusting for the other covariates. Risk of ED visits, readmissions, length of stay during readmission, rehabilitation/SNF visits, outpatient office visits, and telemedicine visits were increased by 57% (RR 1.57; 95% CI 1.53-1.60), 50% (RR 1.50; 95% CI 1.46-1.54), 55% (RR 1.55; 95% CI 1.53-1.56), 18% (RR 1.18; 95% CI 1.14-1.22), 16% (RR 1.16; 95% CI 1.16-1.17), and 28% (RR 1.28; 95% CI 1.24-1.31), respectively. Younger patients (ages 18 to 65 years), women, and Hispanic patients with COPD showed an increased risk for post-discharge HCU. Conclusion: Patients with COPD hospitalized with COVID-19 experienced increased HCU post-discharge compared to patients without COPD.

Cough reflex in lung transplant recipients.

Lung transplantation has become the standard of care for particular individuals with advanced lung disease. However, this surgical procedure involves interruption of the lower vagal nerve fibers which leads to loss of the protective cough reflex. Injury of the neural pathways involved with the sensory limb of the cough reflex is associated with an increased risk of complications involving the allograft. While loss of the cough reflex was once considered permanent, recent evidence indicates functional and structural restoration is a time-dependent process that occurs 6-12 months after lung transplantation. The implication that the cough reflex may be reestablished in lung transplant recipients provides insight into the dynamic response to airway neural injury that may lead to improvements in allograft tissue repair.

Immunohistochemical profile of the pulmonary vasculature in subjects with cirrhosis and histopathologic evidence of pulmonary vascular disease: An autopsy study.

Portopulmonary hypertension (POPH) is a complication of cirrhosis that results in right ventricular failure and death. The objective of this autopsy investigation was to compare pulmonary arterial receptors in subjects with cirrhosis and histopathologic evidence of pulmonary vascular disease (PVD) and control group subjects with cirrhosis lacking evidence of PVD. Autopsy records of 824 subjects with cirrhosis were reviewed to identify pulmonary arterial vasculopathy. Lung sections from paraffin embedded blocks were immunostained for endothelin A (ET-A), endothelin B (ET- B), estrogen α (ER-α), estrogen ß (ER-ß), and vascular endothelial growth factor (VEGF). Subjects with cirrhosis and histopathologic evidence of PVD included 27 individuals with intimal hyperplasia (93%), medial hypertrophy (96%), and plexiform lesions (78%). Immunohistochemical staining for ET-A revealed positive reactivity in 40% of the group with cirrhosis and histopathologic evidence of PVD and 13% of the control group (NS). ET-B reactivity in the pulmonary endothelium and smooth muscle was identified in all subjects with cirrhosis and histopathologic evidence of PVD and control group. VEGF reactivity was identified in the endothelium in all subjects with cirrhosis and histopathologic evidence of PVD compared with 33% of the control group (p = 0.0002). ER-ß reactivity was observed in four subjects (26.6%) with cirrhosis and histopathologic evidence of PVD while none in the control group (NS). Cirrhosis and histopathologic evidence of PVD was found in 3.3% of autopsies with the pulmonary vasculature immunohistochemical profile demonstrating endothelial and smooth muscle reactivity for endothelin, VEGF and ER-ß.

Outcomes With sGC Therapy in Patients With HFpEF: A Meta-Analysis of Prior Trials.

Soluble guanylate cyclase (sGC) agents have been shown to have possible beneficial effects in heart failure treatment. Unfortunately, the role of sGC in HFpEF has not been shown to be efficacious based on recent trials. The CAPACITY HFpEF and VITALITY-HFpEF trials independently showed that sGC does not improve 6-minute walk test (6MWT) distance or the Kansas City Cardiomyopathy Questionnaire (KCCQ) physical limitation score (PLS). The objective of this study was to analyze current data on the 6MWT and KCCQ PLS score from trials that included patients with HFpEF treated with sGC. Using MEDLINE and Cochrane databases, meta-analysis and systematic review was performed looking at data in the CAPACITY HFpEF and VITALITY-HFpEF trials.  For safety analysis we evaluated serious adverse events between the CAPACITY HFpEF, VITALITY-HFpEF, SOCRATES-PRESERVED, and DILATE-1trials. A total of 2 trials were analyzed to assess 6MWT and KCCQ score. The total number of combined patients from both trials assessing 6MWT distance in sGC vs placebo therapy were 620 with 309 in the treatment group and 311 in the placebo group. The total number of combined patients from both trials assessing KCCQ score outcomes were 583 with 280 in the treatment group and 303 in the placebo group. A total of 4 trials were evaluated for safety analysis with a total of 987 patients with 529 in the treatment group and 458 in the placebo group. The analysis did not demonstrate significant difference in 6MWT (P = 0.97), KCCQ PLS (P = 0.83), or serious adverse events (P = 0.67).

Pneumonia and Poorly Controlled Diabetes.

CASE PRESENTATION: A 47-year-old man with poorly controlled diabetes mellitus (glycosylated hemoglobin 12%) presented to the ED with a 1-week history of fevers, productive cough, and dyspnea. The patient was febrile and hypoxemic on presentation; laboratory testing was remarkable for hyperglycemia and ketoacidosis. The initial chest CT scan showed right lower lobe consolidation and ground-glass opacities (Fig 1A). He was admitted to the ICU and administered IV antibiotics (cefepime and vancomycin) for the treatment of community-acquired bacterial pneumonia.

Liver transplant recipient with respiratory failure due to pulmonary fibrosis related to telomere disease requiring lung transplantation.

Short telomere syndrome (STS) is characterized as multiorgan dysfunction presenting with unexplained cytopenias, cryptogenic cirrhosis and pulmonary fibrosis. We present a liver transplant recipient that gradually developed hypoxic respiratory failure attributed to idiopathic pulmonary fibrosis associated telomere disease that culminated in a successful single lung transplantation.

HRCT Diagnosis of Pleuroparenchymal fibroelastosis: Report of two cases.

Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia that is often underdiagnosed on computed tomography scans. The disease process involves a combination of fibrosis involving the visceral pleura and fibroelastic changes within the subpleural lung parenchyma. Although definitive diagnosis is based on pathological evaluation, this is often not feasible and pattern recognition on CT as "definite PPFE" or "consistent with PPFE" is important given that sub group of patients will undergo rapid progression with clinical deterioration.

Determining Cause of Death During Coronavirus Disease 2019 Pandemic.

Controversy exists whether the cause of death due to severe acute respiratory syndrome coronavirus 2 is directly related to the infection or to underlying conditions. The purpose of this study is to assess the relationship of severe acute respiratory syndrome coronavirus 2 infection with the cause of death in hospitalized patients. DESIGN: Retrospective observational study; deidentified discharge summaries of deceased patients were reviewed by two intensivists and classified as coronavirus disease 2019-related (caused by severe acute respiratory syndrome coronavirus 2) or coronavirus disease 2019-unrelated (not caused by severe acute respiratory syndrome coronavirus 2 or indeterminate) deaths. For classification disagreement, a separate group of three intensivists reviewed the discharge summaries and arbitrated to determine the cause of death. SETTING: Single-center study performed at the University of Texas Medical Branch. PATIENTS: All adult patients (> 18 yr) admitted from March 10, 2020, to October 22, 2020, with positive severe acute respiratory syndrome coronavirus 2 test results who expired during their hospitalization were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, comorbidities, prescribed medications, and ventilatory support data were collected. Comparison between groups was performed using t test and chi-square test. During the study period, 1,052 patients were admitted within 14 days of severe acute respiratory syndrome coronavirus 2-positive test results, of whom 100 expired during the hospitalization. Deceased patients were predominantly male and older than 65 years. Obesity (body mass index ≥ 30 kg/m2) was present in 41%, and common comorbidities included hypertension (47%), diabetes (30%), and heart failure (20%). Death was classified as directly caused by severe acute respiratory syndrome coronavirus 2 in 85% and not caused by severe acute respiratory syndrome coronavirus 2 in 5%. An indeterminate cause of death in 10% was due to insufficient information or an atypical presentation. The observed interrater agreement on the cause of death classification was 81%. CONCLUSIONS: In this single-center study, the majority of deaths in severe acute respiratory syndrome coronavirus 2-positive hospitalized patients were related to a typical or atypical presentation of coronavirus disease 2019 disease.

Outcomes of Patients with COPD Hospitalized for Coronavirus Disease 2019.

RATIONALE: There is controversy concerning the association of chronic obstructive pulmonary disease (COPD) as an independent risk factor for mortality in patients hospitalized with Coronavirus Disease 2019 (COVID-19). We hypothesize that patients with COPD hospitalized for COVID-19 have increased mortality risk. OBJECTIVE: To assess whether COPD increased the risk of mortality among patients hospitalized for COVID-19. METHODS: We conducted a retrospective cohort analysis of patients with COVID-19 between February 10, 2020, and November 10, 2020, and hospitalized within 14 days of diagnosis. Electronic health records from U.S. facilities (Optum COVID-19 data) were used. RESULTS: In our cohort of 31,526 patients, 3030 (9.6%) died during hospitalization. Mortality in patients with COPD was higher than that of patients without COPD, 14.02% and 8.8%, respectively. Univariate (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.54 to 1.84) and multivariate (OR 1.33; 95% CI 1.18 to 1.50) analysis showed that patients with COPD had greater odds of death due to COVID-19 than patients without COPD. We found significant interactions between COPD and sex and COPD and age. Specifically, the increased mortality risk associated with COPD was observed among female (OR 1.62; 95% CI 1.36 to 1.95) but not male patients (OR 1.14; 95% CI 0.97 to 1.34); and in patients aged 40 to 64 (OR 1.42; 95% CI 1.07 to 1.90) and 65 to 79 (OR 1.48; 95% CI 1.23 to 1.78) years. CONCLUSIONS: COPD is an independent risk factor for death in adults aged 40 to 79 years hospitalized with COVID-19 infection.

Non-CF bronchiectasis: Orphan disease no longer.

Bronchiectasis is a complex, chronic respiratory condition, characterized by frequent cough and exertional dyspnea due to a range of conditions that include inherited mucociliary defects, inhalational airway injury, immunodeficiency states and prior respiratory infections. For years, bronchiectasis was classified as either being caused by cystic fibrosis or non-cystic fibrosis. Non-cystic fibrosis bronchiectasis, once considered an orphan disease, is more prevalent worldwide in part due to greater availability of chest computed tomographic imaging. Identification of the cause of non-cystic fibrosis bronchiectasis with the use of chest imaging, laboratory testing, and microbiologic assessment of airway secretions can lead to initiation of specific therapies aimed at slowing disease progression. Nonpharmacologic therapies such as airway clearance techniques and pulmonary rehabilitation improve patient symptoms. Inhaled corticosteroids should not be routinely prescribed unless concomitant asthma or COPD is present. Inhaled antibiotics prescribed to individuals with >3 exacerbations per year are well tolerated, reduce airway bacteria load and may reduce the frequency of exacerbations. Likewise, chronic macrolide therapy reduces the frequency of exacerbations. Medical therapies for cystic fibrosis bronchiectasis may not be effective in treatment of non-cystic fibrosis bronchiectasis.

Trends and Factors Associated with Nebulized Therapy Prescription in Older Adults with Chronic Obstructive Pulmonary Disease from 2008 to 2015.

Background: Medical management of patients with chronic obstructive pulmonary disease (COPD) includes nebulized therapy as an option for inhalational drug delivery. A broad variety of short- and long-acting bronchodilators and inhaled corticosteroids in the nebulized form are available. Despite this, limited information exists on the pattern and predictors of nebulized prescription. We examined the trend and factors associated with prescription of nebulized therapy among Medicare beneficiaries with COPD. Methods: A retrospective cross-sectional study of 5% Medicare beneficiaries with COPD (n = 66,032) who were enrolled in parts A, B, and D and received nebulized prescription from 2008 to 2015 was conducted. This sample has shown to be representative of the entire fee-for-service Medicare population. The primary outcome was a prescription of nebulized medications. Reliever nebulized medications included short-acting beta agonist (SABA), short-acting muscarinic agents (SAMAs), and a combination of SABA and SAMA, while maintenance nebulized medications included long-acting beta agonists, long-acting muscarinic agents, and corticosteroid solutions as well as combinations of these agents. The secondary outcome was prescription of other inhaler respiratory medications not administered with a nebulizer. Results: Overall, 38.9% patients were prescribed nebulized medication and their prescription significantly declined from 42.4% in 2008 to 35.1% in 2015, majority of which was related to decreased prescriptions of nebulized relievers. Factors associated with the prescription of nebulized medications include female gender (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.02-1.09), dual eligibility or low-income subsidy beneficiaries (OR = 1.49; CI = 1.44-1.53), hospitalization for COPD in the previous year (OR = 1.29; CI = 1.25-1.34), home oxygen therapy (OR = 2.29; CI = 2.23-2.36), pulmonary specialist visit (OR = 1.24; CI = 1.20-1.27), and moderate (OR = 1.61; CI = 1.57-1.65) or high (OR = 1.52; CI = 1.46-1.59) severity of COPD. Conclusion: Between 2008 and 2015, prescriptions for nebulized therapy for COPD declined among Medicare beneficiaries, probably related to increase in use of maintenance non-nebulized medications.

Discordant bilateral bronchoalveolar lavage findings in a patient with acute eosinophilic pneumonia associated with counterfeit tetrahydrocannabinol oil vaping.

Vaping has emerged as a popular alternative form of inhalation of nicotine and marihuana derivates (including Tetrahydrocannabinol, THC) in part due to the avoidance of combustion byproducts. Unfortunately, THC oil (especially that produced by unregulated individuals) may contain dilutants such as propylene glycol, vitamin E, and flavoring ingredients that can lead to adverse respiratory effects. Acute eosinophilic pneumonia (AEP) has been described in association with e-cigarette and vaping associated lung injury (EVALI) but the majority of bronchoalveolar lavage (BAL) samples reported in the literature do not show eosinophils as the predominant cell lineage. Only two other cases of AEP have been published, and here we present the first case reported in the literature of a patient with EVALI with AEP pattern associated with counterfeit tetrahydrocannabinol (THC) oil vaping and discordant bilateral BAL cell count differential.

Spirometry Measurement of Peak Inspiratory Flow Identifies Suboptimal Use of Dry Powder Inhalers in Ambulatory Patients with COPD.

OBJECTIVES: Determine the prevalence of suboptimal peak inspiratory flow rate (PIFR) and associated patient characteristics and compare PIFR measurements obtained with spirometry and In-Check DIAL® device in ambulatory patients with COPD. METHODS: Patients underwent PIFR measurement with In-Check DIAL® device and pulmonary function testing with calibrated equipment. Group characteristics and lung function were compared for patients with suboptimal (≤ 60 L/min) and optimal (> 60 L/min) PIFR. Receiver operating curve analysis determined the best maximal forced inspiratory flow (FIF max) value in identifying optimal PIFR by gender and height. RESULTS: From July 1, 2016 to January 31, 2018, a total of 303 patients with chronic obstructive pulmonary disease (COPD) had PIFR and pulmonary function measurements. Group mean age was 65.5 ± 11.3 years with equal gender distribution. Suboptimal PIFR was observed in 61 (20.1%) patients. A significant correlation was observed between PIFR and FIF max, inspiratory capacity and residual volume (RV) to total lung capacity (TLC) ratio. In the suboptimal PIFR group, mean FIF max measured by spirometry was significantly less compared with the optimal PIFR group; 178.5 ± 56.9 L/min and 263.4 ± 89.9 L/min, respectively (p<0.0001). Receiver operator curve analysis of FIF max to identify an optimal PIFR yielded an area under the curve of 0.79. Males < 65 inches had a suboptimal PIFR in 16.7 % of the male cohort, while females < 65 inches had a suboptimal PIFR in 27.4 % of the women. CONCLUSIONS: Suboptimal PIFR was present in 1 in 5 stable patients with COPD and was more frequent in short statured females. Spirometry determined FIF max was associated with PIFR based on gender and height.

Restoration of cough reflex in lung transplant recipients.

BACKGROUND: Lung transplantation involves vagal nerve interruption resulting in sensory airway denervation and impairment of the cough reflex. Following lung transplantation, it is unclear whether functional recovery of the cough reflex occurs over time. Our objective was to evaluate the afferent limb of the cough reflex in lung transplant recipients. METHODS: The assessment of cough reflex involved upper airway anesthesia, conscious sedation, and fiberoptic bronchoscopy; the biopsy forceps and a 5% dextrose solution were applied through the bronchoscope to the airway mucosa at the main carina, proximal and distal to the anastomosis. A cross-sectional group of seven subjects underwent a single assessment, while eight subjects in a longitudinal group underwent assessment at 1.5 and 12 months. Cough frequency was determined by counting the number of audible coughs and abdominal muscle contractions measured with a surface electromyogram recorder. The airway anastomosis from deceased subjects in the longitudinal group was examined for nerves. RESULTS: All seven subjects from the cross-sectional group demonstrated a similar cough frequency after mechanical and chemical irritation of all airway sites. All subjects in the longitudinal group who were evaluated at 1.5 weeks had a cough response at all sites except distal to the anastomosis. Twelve months after transplantation, cough was present at all sites. Immunohistochemical staining for protein gene product 9.5, low-affinity neurotrophin, and vanilloid receptors demonstrated nerves in subepithelial regions proximal and distal to the airway anastomosis. CONCLUSION: In human lung transplant recipients, recovery of the cough reflex was noted 12 months after lung transplantation.