Successful and safe treatment of severe steroid depended eosinophilic asthma with mepolizumab in a woman during pregnancy.

A 26-year-old female with steroid dependent eosinophilic asthma and nasal polyps who had successfully been treated with mepolizumab for 17 consecutive months with complete steroid withdrawal and symptoms control, stopped biologic treatment due to pregnancy efforts. Mepolizumab discontinuation resulted in frequent exacerbations and daily symptoms despite high dose ICS/LABA and re-initiation of oral steroids. Mepolizumab was initiated again, followed by improvement of asthma control and gradual withdrawal of steroids within 2 months. The patient became pregnant during the fourth month of mepolizumab re-initiation. The patient presented two asthma exacerbations during pregnancy treated with short course (3 days) oral steroids and delivery was uneventful (female, Apgar 9, weight 2750 g, length 59 cm) in week 40 by caesarean section.

Ventilatory efficiency in combination with peak oxygen uptake improves risk stratification in patients undergoing lobectomy.

Objective: We aimed to evaluate whether or not using the slope of the increase in minute ventilation in relation to carbon dioxide (VE/VCo2-slope), with a cutoff value of 35, could improve risk stratification for major pulmonary complications or death following lobectomy in lung cancer patients at moderate risk (Vo2peak = 10-20 mL/kg/min). Methods: Single center, retrospective analysis of 146 patients with lung cancer who underwent lobectomy and preoperative cardiopulmonary exercise testing in 2008-2020. The main outcome was any major pulmonary complication or death within 30 days of surgery. Patients were categorized based on their preoperative cardiopulmonary exercise testing as: low-risk group, peak oxygen uptake >20 mL/kg/min; low-moderate risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope <35; and moderate-high risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope ≥35. The frequency of complications between groups was compared using χ2 test. Logistic regression was used to calculate the odds ratio with 95% CI for the main outcome based on the cardiopulmonary exercise testing group. Results: Overall, 25 patients (17%) experienced a major pulmonary complication or died (2 deaths). The frequency of complications differed between the cardiopulmonary exercise testing groups: 29%, 13%, and 8% in the moderate-high, low-moderate, and low-risk group, respectively (P = .023). Using the low-risk group as reference, the adjusted odds ratio for the low-moderate risk group was 3.44 (95% CI, 0.66-17.90), whereas the odds ratio for the moderate-high risk group was 8.87 (95% CI, 1.86-42.39). Conclusions: Using the VE/VCo2-slope with a cutoff value of 35 improved risk stratification for major pulmonary complications following lobectomy in lung cancer patients with moderate risk based on a peak oxygen uptake of 10 to 20 mL/kg/min. This suggests that the VE/VCo2-slope can be used for preoperative risk evaluation in lung cancer lobectomy.

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

Thoracoscopic right middle lobe subsegmentectomy: A single-center, retrospective review.

Objective: The right middle lobe subsegmentectomy (including multisubsegmentectomy and subsubsegmentectomy) has never been reported. This study aimed to describe a thoracoscopic right middle lobe subsegmentectomy. Methods: This retrospective study included 94 patients who underwent thoracoscopic right middle lobe subsegmentectomy between August 2018 and February 2021. All procedures were performed with the help of the preoperative 3-dimensional computed tomography bronchography and angiography. Results: Ninety-four patients underwent thoracoscopic right middle lobe subsegmentectomy. The median operative time was 56 minutes (range, 35-86 minutes) and median blood loss was 86 mL (range, 50-150 mL). The median duration of chest tube retention was 2.5 days (range, 1-4 days). There were neither cases of postoperative right middle lobe torsion nor instances of perioperative death. The median size of the tumor in the resected segment was 1.3 cm (range, 1.1-1.8 cm). The median margin was 3.3 cm (range, 2.9-4.3). There were 88 cases of lung cancer and 6 cases of benign lesions. The median number of N1 lymph nodes sampled was 3 (range, 2-4). No lymph node involvement was observed postoperatively. No recurrence or mortality was observed during the median follow-up period of 26 months (range, 6-36 months). Conclusions: Thoracoscopic right middle lobe subsegmentectomy is feasible and safe. It may be valuable to preserve the lung parenchyma in patients with noninvasive lung cancer, multiple lung cancer, and benign diseases. Long-term lung function, survival, and cancer-free data are being collected.

Use of estrogen supplementation is associated with higher quality of life scores in women with cystic fibrosis.

The association of estrogen supplementation use and quality of life in women with cystic fibrosis (CF) is not well characterized. In this cross-sectional study, women with CF completed quality of life questionnaires during a routine CF clinic visit. The use of estrogen supplementation was associated with higher quality of life scores in all domains of the CF questionnaire-revised (CFQ-R) and was significant in the role limitations and respiratory domains. Most participants who were not currently using estrogen supplementation had previously used estrogen supplementation. Most participants had used estrogen to regulate menses, prevent pregnancy and control symptoms around menses. Use of estrogen supplementation was not associated with differences in life-space mobility or screening for sexual dysfunction. This is the largest study to date investigating the association of estrogen supplementation and quality of life in women with CF. Prospective randomized studies are needed to clarify the association of estrogen supplementation and quality of life in women with CF.

A patient case demonstrating the efficacy of benralizumab in uncontrolled severe eosinophilic asthma refractory to omalizumab and mepolizumab treatment.

Severe eosinophilic asthma is associated with a heavy burden and impact on daily living in patients experiencing uncontrolled symptoms, exacerbations, and treatment side effects. This case study reports a 49-year-old woman who presented to the severe asthma center with uncontrolled severe asthma despite multiple maintenance medications and omalizumab treatment. On presentation, the patient had experienced two to three hospitalizations per year, frequent asthma exacerbations requiring courses of oral corticosteroids, and symptoms that impacted her quality of life. Omalizumab was previously discontinued, and bronchial thermoplasty was also unsuccessful. The patient stabilized on injectable steroids and commenced mepolizumab once available on prescription. Owing to continued exacerbations and an inability to reduce steroid treatment without exacerbating, mepolizumab was discontinued and the patient commenced benralizumab (30 mg subcutaneously every 4 weeks for the first three doses, every 8 weeks thereafter) under the sole care of the severe asthma center. Benralizumab treatment resulted in a reduction in steroid treatment, zero asthma exacerbations, improved asthma control and lung function, and a marked improvement in activity levels that allowed the patient to participate in a long-distance running event. Additionally, 7 months following the initiation of benralizumab treatment, her blood eosinophils were completely depleted. These findings support the use of benralizumab in patients with refractory uncontrolled severe eosinophilic asthma despite previous biologic treatment with omalizumab and mepolizumab, as improvements in clinical and patient outcomes, including quality of life, can be achieved in difficult-to-treat cases.

Indocyanine green imaging for pulmonary segmentectomy.

OBJECTIVE: Delineation of the intersegmental plane during pulmonary segmentectomy by systemic injection of indocyanine green (ICG) has been rapidly emerging. We evaluated the feasibility of the use of ICG in a large-scale cohort according to the type of segmentectomy and the presence of obstructive lung disorder and compared the demarcation status with air injection. METHODS: We collected the data of 209 patients who underwent segmentectomy using ICG at National Cancer Center Hospital, Tokyo, Japan. Data of the operation including the demarcation status of the intersegmental plane were analyzed retrospectively. RESULTS: The median operation duration and blood loss were 105 minutes (interquartile range, 94-118 minutes) and 12 mL (interquartile range, 5-24 mL), respectively. Good demarcation of the intersegmental plane by ICG was observed in 184 (88.0%) cases, with no correlation to the type of resected segments or the presence of obstructive lung disorder. Postoperative complications of Clavien-Dindo classification grade 3 or more were observed in 5 cases (2.4%), and no ICG-related adverse event was noted. High-frequency jet ventilation was also used in 160 cases (76.6%) to delineate the intersegmental inflation-deflation plane. The air injected by high-frequency jet ventilation tended to spread further beyond the intersegmental plane that was depicted by ICG. CONCLUSIONS: The use of ICG might demarcate the intersegmental plane more restricted to the target segment compared with air injection. Delineation of the intersegmental plane by ICG is feasible regardless of the type of segmentectomy or the presence of obstructive lung disorder, and it can be commonly applicable in pulmonary segmentectomy.

Building consensus on inpatient discharge pathway components in the management of blunt thoracic injuries: An e-Delphi study amongst an international professional expert panel.

INTRODUCTION: Access to a standardised and evidence informed approach to blunt thoracic injury (BTI) management remains challenging across organised trauma systems globally. It remains important to optimise recovery through pathway-based interventions. The aim of this study was to identify components of care that are important in the effective discharge process for patients with BTI and pinpoint core and optional components for a patient pathway-based intervention. METHODS: Components of care within the hospital discharge process after BTI were identified using existing literature and expert opinion. These initial data were entered into a three-round e-Delphi consensus method where round one involved further integrating and categorising components of discharge care from the expert panel. The panel comprised of an international interdisciplinary group of healthcare professionals with experience in the management of BTI. All questionnaires were completed anonymously using an online survey and involved rating care components using Likert scales (Range: 1-6). The final consensus threshold for pathway components were defined as a group rating of greater than 70% scoring in either the moderate importance (3-4) or high importance category (5-6) and less than 15% of the panel scoring within the low importance category (1-2). RESULTS: Of 88 recruited participants, 67 (76%) participated in round one. Statements were categorised into nine themes: (i) Discharge criteria; (ii) Physical function and Self-care; (iii) Pain management components; (iv) Respiratory function components; (v) General care components; (vi) Follow-up; (vii) Psychological care components; (viii) Patient, family and communication; (ix) 'Red Flag' signs and symptoms. Overall, 70 statements were introduced into the consensus building exercise in round two. In round three, 40 statements from across these categorises achieved consensus amongst the expert panel, forming a framework of core and optional care components within the discharge process after BTI. CONCLUSIONS: These data will be used to build a toolkit containing guidance on developing discharge pathways for patients with BTI and for the development of audit benchmarks for analysing healthcare provision in this area. It is important that interventions developed using this framework are validated locally and evaluated for efficacy using appropriate research methodology.

Impact of postoperative pleurodesis on pulmonary function after lung segmentectomy.

Objective: Pleurodesis is among several treatment strategies for postoperative alveolo-pleural fistula (APF) after lung resection. Accordingly, the present study aimed to determine the influence of pleurodesis on postoperative pulmonary function. Methods: Patients who underwent anatomical segmentectomy between January 2009 and March 2020 and pulmonary function tests 6 and 12 months after initial surgery were included in this study. Differences in pulmonary function decline between patients who did and did not undergo pleurodesis were compared. Results: Among the 319 patients included, 39 (12.2%) underwent pleurodesis. Among patients who did not receive pleurodesis, there were no difference in decline of vital capacity at 6 months (-13.7% ± 1.1% vs -11.2% ± 0.7%; P = .063) and 12 months (-10.7% ± 1.3% vs -9.5% ± 0.7%; P = .391) after surgery between patients who had APF on postoperative day 2 and those who did not. Patients who received pleurodesis had a significantly larger decline in vital capacity at 6 months (-19.4% ± 2.4% vs -13.7% ± 1.1%; P = .015) and 12 months (-16.2% ± 1.6% vs -10.7% ± 1.3%; P = .010) after surgery compared with those who had APF on postoperative day 2 and did not receive pleurodesis. There were no significant differences in decline of forced expiratory volume in 1 second. Conclusions: Pleurodesis negatively influenced postoperative vital capacity after lung segmentectomy. Although the clinical influence of this is unknown, careful consideration is needed before performing pleurodesis given its potential influence on postoperative pulmonary function.

Longstanding tracheobronchomalacia: A forgotten cause of severe cough and its response to roflumilast.

This case report describes a patient with moderately severe tracheobronchomalacia following mycoplasma pneumonia. The patient was considered to have obstructive lung disease despite no prior smoking or lung disease and failure to respond to standard treatment. The possibility of tracheal pathology causing cough and sputum was not considered in 23yrs confirming this to be a "forgotten zone". The patient was treated with Roflumilast to reduce airway secretions with great success and the Immunology of Roflumilast is discussed.

Medical devices in allergy practice.

Medical devices provide people with some health benefits in terms of diagnosis, prevention, treatment, and monitoring of disease processes. Different medical specialties use varieties of medical devices more or less specific for them. Allergology is an interdisciplinary field of medical science and teaches that allergic reactions are of systemic nature but can express themselves at the level of different organs across the life cycle of an individual. Subsequently, medical devices used in allergology could be regarded as: 1) general, servicing the integral diagnostic and management principles and features of allergology, and 2) organ specific, which are shared by organ specific disciplines like pulmonology, otorhinolaryngology, dermatology, and others. The present position paper of the World Allergy Organization (WAO) is meant to be the first integral document providing structured information on medical devices in allergology used in daily routine but also needed for sophisticated diagnostic purposes and modern disease management. It is supposed to contribute to the transformation of the health care system into integrated care pathways for interrelated comorbidities.

Oral ethinyl estradiol treatment in women with cystic fibrosis is associated with lower bone mineral density.

OBJECTIVE: The purpose of this study was to determine whether estrogen supplementation primarily from oral contraceptive pills compared to no estrogen supplementation is associated with differences in mean bone mineral density (BMD) measured by DXA in a cross-sectional study of women with cystic fibrosis (CF). METHODS: In this cross-sectional study of women with CF followed at a single center, we analyzed 49 women with CF ages 18-50 years with a documented DXA. BMD of women with CF taking estrogen supplementation was compared to BMD of women with CF not taking estrogen supplementation. RESULTS: Twelve women with CF were taking estrogen supplementation with mean dose of 23.3 mcg/day (SD 6.9 mcg/day) of ethinyl estradiol. There were no statistically significant differences between demographics of the 12 women with CF taking estrogen supplementation compared to the 37 women with CF not taking estrogen supplementation. Women taking estrogen had lower mean lumbar spine Z-score: -0.7 ± 0.7, compared to women not taking estrogen, Z-score: -0.04 ± 1.0 (p-value 0.046). Women taking estrogen had lower mean BMD at the lumbar spine: 0.952 ± 0.086 g/cm2, compared to women not taking estrogen: 1.023 ± 0.105 g/cm2 (p-value 0.038). Similar trends were seen at the total hip and femoral neck. CONCLUSION: Low-dose estrogen supplementation in premenopausal women with CF was associated with lower BMD compared to no estrogen supplementation in a similar group of premenopausal young women with CF. Future studies are needed to investigate the optimal formulation, route of administration, and dose to accrue and preserve bone mass in premenopausal women with CF.

Long-term clinical prognosis of human infections with avian influenza A(H7N9) viruses in China after hospitalization.

BACKGROUND: Mainland China has experienced five epidemics of human cases of avian influenza A(H7N9) virus infection since 2013. We conducted a prospective study to assess long-term clinical, pulmonary function testing, and chest computed tomography (CT) imaging findings after patients were discharged from hospital. METHODS: A(H7N9) survivors in five provinces and one municipality underwent follow-up visits from August 2013 to September 2018, at three, six, and 12 months after illness onset, and a subset was also assessed at 18 and 64 months after onset. Thirteen patients were enrolled from the first A(H7N9) epidemic in 2013, 36 from the 2013-2014 second epidemic, and 12 from the 2016-2017 fifth epidemic. At each visit, A(H7N9) survivors received a medical examination, including the mMRC (modified Medical Research Council) dyspnea scale assessment, chest auscultation, pulmonary function testing and chest CT scans. FINDINGS: The median age of 61 A(H7N9) survivors was 50 years. The cumulative rate of pulmonary dysfunction was 38·5% and 78·2% for chest CT scan abnormalities at the end of follow-up. Restrictive ventilation dysfunction was common during follow-up. Mild dyspnea was documented at three to 12-month follow-up visits. INTERPRETATION: Patients who survived severe illness from A(H7N9) virus infection had evidence of persistent lung damage and long-term pulmonary dysfunction. FUNDING: National Science Fund for Distinguished Young Scholars (grant number 81525023); Program of Shanghai Academic/Technology Research Leader (grant number 18XD1400300); National Science and Technology Major Project of China (grant numbers 2017ZX10103009-005, 2018ZX10201001-010).

Intraoperative oxygen challenge for toleration of single lung ventilation in a patient with severe obstructive airway disease: A case report.

Perioperative risk assessment is complex in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery. A 70-year-old female with severe chronic obstructive pulmonary disease and previous right middle and lower lobectomy, presented for left lower lobe superior segmentectomy. Respiratory function tests revealed a forced expiratory volume in 1 second of 0.72L, a forced vital capacity of 1.93L, and a carbon monoxide transfer factor of 10.0 ml/min/mmHg. A cardiopulmonary exercise test demonstrated little ventilatory reserve with profound arterial desaturation on peak exercise, however, a normal peak oxygen consumption (16.7 ml/min/kg) and a nadir minute ventilation/carbon dioxide slope of 24 implied a limited risk of perioperative cardiovascular morbidity. Given these conflicting results we performed an intraoperative oxygen challenge test under general anaesthesia with sequential ventilation of different lobes of the lung. We demonstrate the use of the oxygen challenge test as an effective intervention to further assess safety and tolerance of anaesthesia of patients with limited respiratory reserve being assessed for further complex redo lung resection surgery. Further, this test was a risk stratification tool that allowed informed decisions to be made by the patient about therapeutic options for treating their lung cancer. The prognostic value of traditional physiological parameters in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery is uncertain. The intraoperative oxygen challenge test is another risk stratification tool to assist clinicians in assessment of safety and tolerance of anaesthesia for patients being considered for lung resection.

Loneliness and ED Visits in Chronic Obstructive Pulmonary Disease.

The primary objective of this study was to investigate the association of loneliness and the incidence of ED visits in a large and well-characterized cohort of patients with severe chronic obstructive pulmonary disease (COPD); the association of loneliness with performance measures and health perception was the secondary objective. Baseline data were used from the National Emphysema Treatment Trial (NETT), which investigated the effectiveness of lung volume reduction surgery in patients with moderate-to-severe COPD. Patients received Quality of Wellbeing questionnaires, which asked about loneliness and social isolation. For comparing baseline variables between lonely and non-lonely subjects, we used χ2 tests for categorical variables and Wilcoxon tests for continuous variables. The association of loneliness with ED visits and health perception was assessed with a logistic model that adjusted for multiple critical confounders. The study took place from December 2002, to December 2004, with a follow-up period of 5 years to assess loneliness and 24 months to assess use of the emergency department. There were 1218 patients analyzed, mean age 65 (standard deviation [SD] 12), 47% were women, FEV 1% 41 (SD 12); 7.9% of participants reported feeling lonely. These individuals had worse health ratings, 6-minute walk tests (6MWTs), and breathlessness. Loneliness was independently associated with ED visits after adjusting for age, lung function, dyspnea, 6MWT, treatment, and gender, odds ratio (OR) 1.57 (95% confidence interval [CI], 1.005-2.466), P=.04. This study suggests that loneliness in patients with COPD is significantly and independently associated to ED visits and reduced health perception. Addressing loneliness of patients with COPD in the outpatient setting may contribute to improved health perception and less health care utilization.

Löffler syndrome on a Louisiana pig farm.

Löffler syndrome, a fulminant eosinophilic pneumonitis associated with the larval migratory phase of human parasites, is rarely reported in the United States. A previously healthy 8-year-old male was hospitalized with tachypnea, cough, hypoxemia, and fever of one week's duration. History revealed exposure to pigs on his family's farm in southernmost Louisiana, where the patient was responsible for cleaning the farm's pigpens. His fingernails were soiled and extremely short, with the edge of the nail bed exposed secondary to onychophagia. Laboratory evaluation demonstrated peripheral eosinophilia (39%), pulmonary eosinophilia (86%), high total IgE, diffuse reticulonodular lung opacities, and mixed obstructive and restrictive pulmonary function pattern. Systemic corticosteroids were initiated for his acute respiratory insufficiency and produced rapid clinical improvement. Serum Ascaris-specific IgE was markedly elevated and he was treated with albendazole. An extensive evaluation for other infectious and allergic etiologies was negative. A site visit to the family farm and laboratory investigation was coordinated with the Louisiana Animal Disease Diagnostic Laboratory at LSU. Ascaris suum eggs were detected in fresh pig feces and in the soil immediately surrounding the pens. Ascariasis should be considered even in the absence of travel history, especially in swine raising areas that are endemic for Ascaris in pigs, such as the southeastern United States. Onychophagia is a highly probable mechanism of zoonotic fecal-oral transmission in this case, and such habits could lead to continual reinfection. Systemic corticosteroids were effective in treating the patient's acute respiratory compromise due to Löffler syndrome.

The road for survival improvement of cystic fibrosis patients in Arab countries.

Cystic fibrosis (CF) is a lethal, monogenic disorder that affects multiple organ systems of the body. The incidence has been described before in the Middle East to be 1 in 2000 to 1 in 5800 live births, and the median survival was estimated to be from 10 to 20 years of age. The present article attempts to revisit various facets of this disease and specifically highlights the most important lacunae that exist in treating CF. In addition, it also tries to emphasize the steps in improving the median survival of patients with CF, in these countries.

Distinct immunologic and radiographic patterns in etanercept-induced lung injury.

Nonspecific clinical presentation of non-infectious, immune-mediated pulmonary complications of etanercept therapy makes the diagnosis difficult. While bronchoalveolar lavage fluid (BALF) cell analysis is frequently used in diagnosing drug-induced lung disease, BALF patterns in etanercept-induced lung injury (EILI) are not well established. Furthermore, previous reports of EILI diagnosis relied on transbronchial or surgical lung biopsies. Here, we report two patients who developed pulmonary toxicity after etanercept treatment. Both patients were diagnosed with EILI. While one patient presented with CD4(+)-predominant lymphocytic alveolitis (consistent with a sarcoid-like pattern), the other patient exhibited a CD8(+)-predominant pattern (consistent with hypersensitivity pneumonitis-like reaction). The different BAL patterns were accompanied by distinct radiographic findings. Both patients significantly improved after etanercept discontinuation and corticosteroid initiation. We propose that EILI can present with distinct immunologic and radiographic phenotypes. In addition, early BALF analysis with lymphocyte immunophenotyping can further define the underlying immunologic abnormalities, and thereby, avoid more invasive procedures.

Exacerbations of chronic obstructive pulmonary disease and chronic mucus hypersecretion.

Chronic obstructive pulmonary disease (COPD) exacerbations are an important cause of the considerable morbidity and mortality found in COPD. COPD exacerbations increase with increasing severity of COPD, and some patients are prone to frequent exacerbations leading to hospital admission and readmission. These frequent exacerbations may have considerable impact on quality of life and activities of daily living. Factors that increase the risk for COPD exacerbations are associated with increased airway inflammation caused by common pollutants and bacterial and/or viral infections. These inflammatory responses cause mucus hypersecretion and, thereby, airway obstruction and associated exacerbations. While chronic mucus hypersecretion is a significant risk factor for frequent and severe exacerbations, patients with chronic mucus hypersecretion have a lower rate of relapse after initial treatment for acute exacerbation. The benefit of antibiotics for treatment of COPD exacerbations is small but significant. While the mechanisms of actions are not clear, mucolytic agents reduce the number of days of disability in subjects with exacerbations. Reducing mucous cell numbers in small airways could be a useful way to reduce chronic mucus hypersecretion. Our studies suggest that programmed cell death is crucial in the resolution of metaplastic mucous cells, and understanding these mechanisms may provide novel therapies to reduce the risk of COPD exacerbations.