Acute Exacerbations In Chronic Obstructive Pulmonary Disease Research Articles

Bacterial Vaccinations in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a frequent, often progressive, chronic disease of the lungs. Patients with COPD often have impaired immunity; therefore, they are prone to chest infections, such as pneumonia or bronchitis. Acute exacerbations of COPD are major events that accelerate disease progression, contributing to its symptoms' burden, morbidity, and mortality. Both pneumonia and acute exacerbations in COPD are caused by bacteria against which there are effective vaccinations. Although the number of randomised controlled studies on bacterial vaccinations in COPD is limited, national and international guidelines endorse specific vaccinations in patients with COPD. This review will summarise the different types of vaccinations that prevent pneumonia and COPD exacerbations. We also discuss the results of early phase studies. We will mainly focus on Streptococcus pneumoniae, as this bacterium was predominantly investigated in COPD. However, we also review studies investigating vaccinations against Haemophilus influenzae, Moraxella catarrhalis, and Bordetella pertussis.

Transcriptomic characterization of the human segmental endotoxin challenge model

Segmental instillation of lipopolysaccharide (LPS) by bronchoscopy safely induces transient airway inflammation in human lungs. This model enables investigation of pulmonary inflammatory mechanisms as well as pharmacodynamic analysis of investigational drugs. The aim of this work was to describe the transcriptomic profile of human segmental LPS challenge with contextualization to major respiratory diseases. Pre-challenge bronchoalveolar lavage (BAL) fluid and biopsies were sampled from 28 smoking, healthy participants, followed by segmental instillation of LPS and saline as control. Twenty-four hours post instillation, BAL and biopsies were collected from challenged lung segments. Total RNA of cells from BAL and biopsy samples were sequenced and analysed for differentially expressed genes (DEGs). After challenge with LPS compared with saline, 6316 DEGs were upregulated and 241 were downregulated in BAL, but only one DEG was downregulated in biopsy samples. Upregulated DEGs in BAL were related to molecular functions such as “Inflammatory response” or “chemokine receptor activity”, and upregulated pro-inflammatory pathways such as “Wnt-"/“Ras-"/“JAK-STAT” “-signaling pathway”. Furthermore, the segmental LPS challenge model resembled aspects of the five most prevalent respiratory diseases chronic obstructive pulmonary disease (COPD), asthma, pneumonia, tuberculosis and lung cancer and featured similarities with acute exacerbations in COPD (AECOPD) and community-acquired pneumonia. Overall, our study provides extensive information about the transcriptomic profile from BAL cells and mucosal biopsies following LPS challenge in healthy smokers. It expands the knowledge about the LPS challenge model providing potential overlap with respiratory diseases in general and infection-triggered respiratory insults such as AECOPD in particular.

The Management of Acute Exacerbations in COPD: A Retrospective Observational Study and Clinical Audit.

(1) Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are not only associated with increased patient morbidity and mortality, but with extensive healthcare costs. Thus, adequate clinical management is crucial. The aim of this project was to evaluate the management of acute COPD exacerbations in a public teaching hospital in Switzerland. (2) Methods: We retrospectively analyzed clinical routine data of patients presenting with an acute exacerbation of COPD at the emergency department of a Swiss hospital between January 2019 and February 2020. Management was evaluated against recommendations from the GOLD 2019 report and previous audits. (3) Results: The data of 184 patients (mean age 73.5 years, range 41-95 years, 53% male) with 226 visits were included. While the documentation of GOLD stage (I-IV) and smoking status was consistent (81.0% and 91.6%), GOLD risk category (A-D) was only documented in 36% of the cases. Patients' respiratory rate upon presentation was measured in 73%, and blood gas analysis was performed in 70%. A total of 94% of the patients received a chest imaging; spirometry was performed in 10%. Initial symptomatic therapy with short acting bronchodilators was applied in 56%. Systemic steroid treatment was installed in 86%. Antibiotics were given in 56%, but in one fourth the indication was not clear. Non-invasive ventilation was applied in 25% of the indicated cases. Smoking cessation was recommended to 26% of the current smokers and referral to pulmonary rehabilitation was given in 16%. (4) Conclusion: GOLD recommendations were not comprehensively implemented, especially with regard to the assessment of severity, initial symptomatic therapy, and non-invasive ventilation. These results show the importance of the frequent revision of routine practice and may help to create awareness among practitioners and ultimately improve the quality of COPD management.

Are We Missing the Opportunity to Disseminate GOLD Recommendations Through AECOPD Discharge Letters?

Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) lead to poor outcomes and increased burden for patients and healthcare systems. The Global Initiative for COPD (GOLD) includes specific recommendations for AECOPD interventions, discharge criteria, and follow-up. Aligning the AECOPD discharge letters (DL) with GOLD guidelines could facilitate dissemination of recommendations among general practitioners (GPs). This study was conducted to assess the compliance of DL with the GOLD recommendations in Croatia. Pre-pandemic DL of patients presenting for AECOPD to emergency room (ER) were analyzed and stratified by clinical decision to hospitalize (HDL) or discharge patients for outpatient treatment (ERDL). Experienced pulmonologists checked the information from DL against guidelines by using online study-specific questionnaires. In total, 225 HDL and 368 ERDL were analyzed. In most cases, the GOLD ABCD categories (85% HDL, 92% ERDL) or the spirometry-based degree of severity (90% HDL, 91% ERDL) were not included. The number of AEs in the previous year was recorded, but the specific frequent exacerbator phenotype not explicitly stated. The AE phenotype was included in two thirds of HDL and one third of ERDL. The blood eosinophil count was frequently available, but not considered decision-relevant information. Adjustments of previous maintenance therapy, mostly escalation, were recommended in 58.4% HDL and 27.9% ERDL, respectively. Education on proper use of inhalers was recommended only in 15.6% of HDL. Smoking cessation measures were advised in 23.1% HDL and 7.9% ERDL; pulmonary rehabilitation in 35.6% HDL and 0.8% ERDL. Early follow-up was frequently advised (>50%), but rarely appointed. Significant deficiencies in compliance with the GOLD guidelines were identified, translating into a missed opportunity for GPs to become acquainted with GOLD recommendations. These findings emphasize the necessity to increase compliance with guidelines first at specialist level and consequent standardization of DL.

Remote Monitoring for Prediction and Management of Acute Exacerbations in Chronic Obstructive Pulmonary Disease (AECOPD).

The progression of chronic obstructive pulmonary disease (COPD) is characterized by episodes of acute exacerbation (AECOPD) of symptoms, decline in respiratory function, and reduction in quality-of-life increasing morbi-mortality and often requiring hospitalization. Exacerbations can be triggered by environmental exposures, changes in lifestyle, and/or physiological and psychological factors to greater or lesser extents depending on the individual’s COPD phenotype. The prediction and early detection of an exacerbation might allow patients and physicians to better manage the acute phase. We summarize the recent scientific data on remote telemonitoring (TM) for the prediction and management of acute exacerbations in COPD patients. We discuss the components of remote monitoring platforms, including the integration of environmental monitoring data; patient reported outcomes collected via interactive Smartphone apps, with data from wearable devices that monitor physical activity, heart rate, etc.; and data from medical devices such as connected non-invasive ventilators. We consider how telemonitoring and the deluge of data it potentially generates could be combined with electronic health records to provide personalized care and multi-disease management for COPD patients.

Day-to-Day Variability of Parameters Recorded by Home Noninvasive Positive Pressure Ventilation for Detection of Severe Acute Exacerbations in COPD.

BackgroundHome noninvasive positive pressure ventilation (NPPV) can be considered not only as an evidence-based treatment for stable hypercapnic chronic obstructive pulmonary disease (COPD) patients, but also as a predictor for detecting severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD).MethodsIn this retrospective observational study, we collected clinical exacerbations information and daily NPPV-related data in a cohort of COPD patients with home NPPV for 6 months. Daily changes in NPPV-related parameters’ variability prior to AECOPD were examined using two-way repeated measures ANOVA and individual abnormal values (>75th or <25th percentile of individual baseline parameters) were calculated during 7-day pre-AECOPD period. Multivariate logistic regression was used to identify the independent risk factors associated with AECOPD that then were incorporated into the nomogram.ResultsBetween January 1, 2018, and January 1, 2020, a total of 102 patients were included and 31 (30.4%) participants experienced hospitalization (AECOPD group) within 6 months. Respiratory rate changed significantly from baseline at 1, 2 or 3 days prior to admission (p<0.001, respectively) in the AECOPD group. The number of days with abnormal values of daily usage, leaks, or tidal volume during the 7-day pre-AECOPD period in the AECOPD group was higher than in the stable group (p<0.001, respectively). On multivariate analysis, 7-day mean respiratory rate (OR 1.756, 95% CI 1.249–2.469), abnormal values of daily use (OR 1.918, 95% CI 1.253–2.934) and tidal volume (OR 2.081, 95% CI 1.380–3.140) within 7 days were independently associated with the risk of AECOPD. Incorporating these factors, the nomogram achieved good concordance indexes of 0.962.ConclusionSeven-day mean respiratory rate, abnormal values of daily usage, leaks, and tidal volume within the 7-day pre-AECOPD period may be biomarkers for detection of AECOPD.

Day-to-day variability of forced oscillatory mechanics for early detection of acute exacerbations in COPD.

Telemonitoring trials for early detection of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have provided mixed results. Day-to-day variations in lung function measured by the forced oscillation technique (FOT) may yield greater insight. We evaluated the clinical utility of home telemonitoring of variability in FOT measures in terms of 1) the relationship with symptoms and quality of life (QoL); and 2) the timing of variability of FOT measures and symptom changes prior to AECOPD. Daily FOT parameters at 5 Hz (resistance (R) and reactance (X); Resmon Pro Diary, Restech Srl, Milan, Italy), daily symptoms (COPD Assessment Test (CAT)) and 4-weekly QoL data (St George's Respiratory Questionnaire (SGRQ)) were recorded over 8-9 months from chronic obstructive pulmonary disease (COPD) patients. Variability of R and X was calculated as the standard deviation (sd) over 7-day running windows and we also examined the effect of varying window size. The relationship of FOT versus CAT and SGRQ was assessed using linear mixed modelling, daily changes in FOT variability and CAT prior to AECOPD using one-way repeated measures ANOVA. Fifteen participants with a mean±sd age of 69±10 years and a % predicted forced expiratory volume in 1 s (FEV1) of 39±10% had a median (interquartile range (IQR)) adherence of 95.4% (79.0-98.8%). Variability of the inspiratory component of X (indicated by the standard deviation of inspiratory reactance (SDXinsp)) related to CAT and weakly to SGRQ (fixed effect estimates 1.57, 95% CI 0.65-2.49 (p=0.001) and 4.41, 95% CI -0.06 to 8.89 (p=0.05), respectively). SDXinsp changed significantly on the same day as CAT (1 day before AECOPD, both p=0.02) and earlier when using shorter running windows (3 days before AECOPD, p=0.01; accuracy=0.72 for 5-day windows). SDXinsp from FOT telemonitoring reflects COPD symptoms and may be a sensitive biomarker for early detection of AECOPD.

Metoprolol is not effective for preventing acute exacerbations in COPD

Results of observational studies suggest that beta-blockers have a role in preventing acute exacerbations of COPD, however a recent randomised controlled trial demonstrates it may cause more harm than good....

Acute exacerbations of COPD and risk of lung cancer in COPD patients with and without a history of asthma

ABSTRACT Rationale There is limited knowledge on the effect of acute exacerbations in chronic obstructive pulmonary disease (AECOPD) on lung cancer risk in COPD patients with and without a history of asthma. This study aims to examine whether AECOPD is associated with risk of lung cancer, and whether the effect depends on a history of asthma. Methods In the GenKOLS study of 2003–2005, 852 subjects with COPD performed spirometry, and filled out questionnaires on smoking habits, symptoms and disease history. These data were linked to lung cancer data from the Cancer Registry of Norway through 2013. AECOPD, measured at baseline was the main predictor. To quantify differences in lung cancer risk, we performed Cox-proportional hazards regression. We adjusted for sex, age, smoking variables, body mass index, and lung function. Measurements and results During follow-up, 8.8% of the subjects with, and 5.9% of the subjects without exacerbations were diagnosed with lung cancer. Cox regression showed a significant increased risk of lung cancer with one or more exacerbations in COPD patients without a history of asthma, HRR = 2.77 (95% CI 1.39–5.52). We found a significant interaction between a history of asthma and AECOPD on lung cancer. Conclusions AECOPD is associated with an increased risk of lung cancer in COPD patients without a history of asthma.

Comparison of machine learning algorithms for the identification of acute exacerbations in chronic obstructive pulmonary disease

ObjectivesIdentifying acute exacerbations in chronic obstructive pulmonary disease (AECOPDs) is of utmost importance for reducing the associated mortality and financial burden. In this research, the authors aimed to develop identification models for AECOPDs and to compare the relative performance of different modeling paradigms to find the best model for this task. MethodsData were extracted from electronic medical records (EMRs) of patients with chronic obstructive pulmonary disease who admitted to the China-Japan Friendship Hospital between February 2011 and March 2017. Five machine learning algorithms (random forest, support vector machine, logistic regression, K-nearest neighbor and naïve Bayes) were used to develop the AECOPDs identification models. Feature selection was performed to find an optimal feature subset. 10-folds cross-validation was used to find the best hyperparameters for each model. The following metrics: area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value were used to evaluate the performance of these models. ResultsA total of 303 EMRs (AECOPDs patients:135; None AECOPDs patients: 168) were included in the study. The SVM model obtained the best performance (sensitivity: 0.80, specificity: 0.83, positive predictive value:0.81, negative predictive value:0.85 and area under the receiver operating characteristic curve: 0.90) after performing feature selection. ConclusionsOur research confirms that the proposed model based on the support vector machine is a powerful tool to identify AECOPDs patients, and it is promising to provide decision support for clinicians when they are struggling to give a confirmed clinical diagnosis.

Telomere length in COPD: Relationships with physical activity, exercise capacity, and acute exacerbations.

RationaleShorter leukocyte telomere length (LTL) is associated with reduced health-related quality of life and increased risk for acute exacerbations (AEs) and mortality in chronic obstructive pulmonary disease (COPD). Increased physical activity and exercise capacity are associated with reduced risk for AEs and death. However, the relationships between LTL and physical activity, exercise capacity, and AEs in COPD are unknown.MethodsData from 3 COPD cohorts were examined: Cohort 1 (n = 112, physical activity intervention trial), Cohorts 2 and 3 (n = 182 and 294, respectively, separate observational studies). Subjects completed a 6-minute walk test (6MWT) and provided blood for LTL assessment using real-time PCR. Physical activity was measured as average daily step count using an accelerometer or pedometer. Number of self-reported AEs was available for 1) the year prior to enrollment (Cohorts 1 and 3) and 2) prospectively after enrollment (all cohorts). Multivariate models examined associations between LTL and average daily step count, 6MWT distance, and AEs.ResultsA significant association between longer LTL and increased 6MWT distance was observed in the three combined cohorts (β = 3x10-5, p = 0.045). No association between LTL and average daily step count was observed. Shorter LTL was associated with an increased number of AEs in the year prior to enrollment (Cohorts 1 and 3 combined, β = -1.93, p = 0.04) and with prospective AEs (Cohort 3, β = -1.3388, p = 0.0003).ConclusionsAmong COPD patients, increased LTL is associated with higher exercise capacity, but not physical activity. Shorter LTL was associated with AEs in a subgroup of cohorts.

Is It Time to Change the Definition of Acute Exacerbation of Chronic Obstructive Pulmornary Disease? What Do We Need to Add?

Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) are associated with increased mortality, rate of hospitalization, use of healthcare resources, and have a negative impact on disease progression, quality of life and lung function of patients with chronic obstructive pulmonary disease (COPD). There is an imperative need to homogenize the definition of AECOPD because the incidence of exacerbations has a significant influence or implication on treatment decision making, particularly in pharmacotherapy and could impact the outcome or change the statistical significance of a therapeutic intervention in clinical trials. In this review, using PubMed searches, we have analyzed the weaknesses and strengths of the different used AECOPD definitions (symptom-based, healthcare-based definition or the combinations of both), as well as the findings of the studies that have assessed the relationship of different biomarkers with the diagnosis, etiology and differential diagnosis of AECOPD and the progress towards the development of a more precise definition of COPD exacerbation. Finally, we have proposed a simple definition of AECOPD, which must be validated in future clinical trials to define its accuracy and usefulness in daily practice.

\u201cI just know\u201d: exploring self-knowledge in chronic obstructive pulmonary disease

The importance of lay knowledge in health care settings, particularly in relation to long-term conditions, has received increasing attention over the past few decades. However, there remains some way to go before patients’ experiential or self-knowledge forms part of current clinical decision making and care provision. Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition which affects people on a daily basis. People living with this condition develop experiential knowledge about their symptoms and are, arguably, best placed to assess these and treat any acute worsening of their condition accordingly. Here we explore how people with COPD articulate their knowledge and make sense of it within the context of their everyday lives. We re-analysed data from a qualitative interview-based study with 44 participants living with moderate to severe COPD using a grounded theory approach. We found that participants focused their attention on symptoms and sensations of the chest while developing an embodied self-awareness that allowed them to assess whether they were experiencing an acute worsening of their condition. Participants appeared confident in using this self-knowledge to distinguish such acute flare ups from the daily variability of their condition, described as good days and bad days. We suggest that people with COPD are very attuned to their bodies despite the vagueness and sometimes seemingly unrelated nature of their symptoms and signs. We argue that self-knowledge should be acknowledged as valid and meaningful by both patients and clinicians. This is particularly important because of the clinical uncertainty about the precise onset and presentation of acute exacerbations in COPD.

COPD Phenotyping Enhances Targeted Treatment

COPD Phenotyping Enhances Targeted Treatment

Association of Serum Magnesium Levels with Frequency of Acute Exacerbations in Chronic Obstructive Pulmonary Disease: A Prospective Study

Background. The course of chronic obstructive pulmonary disease (COPD) is accompanied by acute exacerbations. The purpose of this study is to determine the association of serum magnesium level with acute exacerbations in COPD (COPD-AE). Materials and Methods. Eighty-nine patients hospitalized with COPD-AE were included. Hemogram, biochemical tests, and arterial blood gases were analyzed. Pulmonary function tests were performed in the stable period after discharge. Patients were followed up at 3 monthly periods for one year. Results. Mean age of the patients was 70.4 ± 7.8 (range 47–90) years. Mean number of COPD-AE during follow-up was 4.0 ± 3.6 (range 0–15). On Spearman correlation analysis there were significant negative correlations between number of COPD-AE and predicted FEV1% (P = 0.001), total protein (P = 0.024), globulin (P = 0.001), creatinine (P = 0.001), and uric acid levels (P = 0.036). There were also significant positive correlations between number of COPD-AE and serum magnesium level (P < 0.001) and platelet count (P = 0.043). According to linear regression analysis predicted FEV1% (P = 0.011), serum magnesium (P < 0.001), and globulin (P = 0.006) levels were independent predictors of number of COPD-AE. Conclusions. In this small prospective observational study we found that serum magnesium level during exacerbation period was the most significant predictor of frequency of COPD-AE.

The Saudi Guidelines for the Diagnosis and Management of COPD.

The Saudi Thoracic Society (STS) launched the Saudi Initiative for Chronic Airway Diseases (SICAD) to develop a guideline for the diagnosis and management of chronic obstructive pulmonary disease (COPD). This guideline is primarily aimed for internists and general practitioners. Though there is scanty epidemiological data related to COPD, the SICAD panel believes that COPD prevalence is increasing in Saudi Arabia due to increasing prevalence of tobacco smoking among men and women. To overcome the issue of underutilization of spirometry for diagnosing COPD, handheld spirometry is recommended to screen individuals at risk for COPD. A unique feature about this guideline is the simplified practical approach to classify COPD into three classes based on the symptoms as per COPD Assessment Test (CAT) and the risk of exacerbations and hospitalization. Those patients with low risk of exacerbation (<2 in the past year) can be classified as either Class I when they have less symptoms (CAT < 10) or Class II when they have more symptoms (CAT ≥ 10). High-risk COPD patients, as manifested with ≥2 exacerbation or hospitalization in the past year irrespective of the baseline symptoms, are classified as Class III. Class I and II patients require bronchodilators for symptom relief, while Class III patients are recommended to use medications that reduce the risks of exacerbations. The guideline recommends screening for co-morbidities and suggests a comprehensive management approach including pulmonary rehabilitation for those with a CAT score ≥10. The article also discusses the diagnosis and management of acute exacerbations in COPD.

Viral and bacterial infection in acute asthma and chronic obstructive pulmonary disease increases the risk of readmission

Background and objectiveInfection is as an important trigger for acute asthma and chronic obstructive pulmonary disease (COPD). The aim of this article was to determine the prevalence and impact of virus and bacterial infections in acute asthma and COPD.MethodsSubjects were recruited, within 24 h of hospital admission for acute exacerbations of asthma and COPD. Nose/throat swabs and sputum samples were collected and examined by multiplex polymerase chain reaction for respiratory viruses and cultured for bacteria. The primary outcomes were length of stay (LOS) and readmission to hospital within 60 days.ResultsA total of 199 subjects were recruited (96 had asthma and 103 COPD) for 235 events (36 re‐presented). A virus was detected in 79 subjects (40%), bacteria in 41 (21%), and of these, 18 had both. Rhinovirus A was the most frequently isolated virus. A multivariate analysis was performed to control for confounders. It found that detection of a virus, a virus and bacteria, forced expiratory volume in 1 s (FEV1) and a diagnosis of COPD were all independent predictors of prolonged LOS, while risk of readmission within 60 days was increased with virus infection alone, virus and bacterial infection, lower FEV1 and current smoking.ConclusionsVirus infection, especially in the presence of chronic bacterial infection, is an important determinant of more severe acute exacerbations in both asthma and COPD, and patients with co‐infections are more likely to be readmitted to hospital following their exacerbation.

Pharmacotherapeutic Approaches to Preventing Acute Exacerbations of Chronic Obstructive Pulmonary Disease

The significance of acute exacerbations in chronic obstructive pulmonary disease (AECOPDs) is increasingly appreciated. AECOPDs result in significant morbidity and mortality and are a significant driver of health care costs. Frequent AECOPDs are associated with poor quality of life and more rapid decline in lung function. As such, reducing their frequency or severity is a key paradigm of COPD therapy. Bronchodilators alone and in combination with inhaled corticosteroids are the current standards of care and decrease AECOPDs. Prevention of infection with chronic macrolide antibiotics or pulsed quinolones has demonstrated some promise. Vaccination against Streptococcus pneumonia and influenza is likely beneficial. Therapeutics with antiinflammatory properties, including phosphodiesterase enzyme 4 inhibitors and HMG-CoA reductase inhibitors, may reduce AECOPD frequency. Inhibiting the formation of reactive oxidant species has also been studied, with varying results. Antioxidants, including N-acetylcysteine and S-carbomethylcysteine, may reduce exacerbation frequency, but further investigation is needed. As new therapies are developed, it will be helpful to know in which patient phenotypes they are most effective and how they compare in efficacy and side-effect profiles with inhaled coricosteroids, bronchodilators, or their combination.

A new strategy with proton pump inhibitors for the prevention of acute exacerbations in COPD

Acute exacerbations of chronic obstructive pulmonary disease (COPD), an acute worsening of respiratory symptoms, generally result in a poor prognosis. Successful prevention and management of such exacerbations is thus important for patient care. Viral infection, primarily with rhinovirus (RV), is the foremost cause of exacerbations in COPD patients. Proton pump inhibitors (PPIs) have been reported to inhibit RV infection in human airway epithelial cells invitro. Furthermore, clinical trials of PPIs in patients with COPD resulted in a reduction in rates of both common cold and COPD exacerbations. In this review, we discuss the significance of COPD exacerbations, summarize a published trial of the effect of low-dose PPIs on COPD exacerbations, and postulate a mechanism for this effect.

Acute Exacerbations in COPD and Their Control with Oral Immunization with Non-Typeable Haemophilus Influenzae

Chronic obstructive pulmonary disease (COPD) a term based on the demonstration of irreversible airways obstruction, introduced to unify a range of chronic progressive diseases of the airways consequent upon inhalation of toxins. While disease is initiated and progressed by inhaled toxins, an additional pathway of damage has emerged, with particular relevance to acute exacerbations. Exacerbations of disease due to an increase in the level of intrabronchial inflammation have taken on a new significance as their role in determining both acute and chronic outcomes is better understood. This “second pathway” of disease is a consequence of bacterial colonization of damaged airways. Although bacteria have been linked to acute episodes in COPD over 50 years, only recently has quality data on antibiotic usage and the detection of “exacerbation isolates” of non-typeable Haemophilus influenzae (NTHi) provided strong argument in support of a pathogenic role. Yet a poor correlation between detection of colonizing bacteria and clinical status remained a concern in attempts to explain a role for bacteria in a classical infection model. This presentation discusses a hypothesis that acute exacerbations reflect a T cell-dependent hypersensitivity response to colonizing bacteria, with IL-17 dependent accumulation of neutrophils within the bronchus, as the main outcome measure. Critical protection against exacerbations following oral administration of NTHi, an immunotherapy that drives a TH17 T cell response from Peyer’s patches, reduces the load of intrabronchial bacteria while preventing access of inhaled bacteria into small airways. Immunotherapy augments a physiological “loop” based on aspiration of bronchus content into the gut. A second “hypersensitivity” mechanism may cause bronchospasm – in both COPD and treatment-resistant asthma – due to specific IgE antibody directed against colonizing bacteria, as oral NTHi abrogates wheeze in subjects with recurrent “wheezy bronchitis.”