Vocal cord dysfunction/inducible laryngeal obstruction cannot be diagnosed from symptoms.

Vocal cord dysfunction/inducible laryngeal obstruction is highly variable. Standard clinical symptoms and questionnaires cannot predict laryngoscopic diagnosis in a "lung disease" population. https://bit.ly/3QUtsbB.

Elevated blood lactate in COPD exacerbations associates with adverse clinical outcomes and signals excessive treatment with ß2 -agonists.

BACKGROUND AND OBJECTIVE: Raised blood lactate secondary to high dose ß2 -agonist treatment has been reported in asthma exacerbations but has not been investigated during acute exacerbations of COPD (AECOPD). We explored associations of blood lactate measurements with disease outcomes and ß2 -agonist treatments during AECOPD. METHODS: Retrospective (n = 199) and prospective studies (n = 142) of patients hospitalized with AECOPD were conducted. The retrospective cohort was identified via medical records and the prospective cohort was recruited during hospitalization for AECOPD. Baseline demographics, comorbidities, ß2 -agonist treatment, biochemical measurements and clinical outcomes were compared between patients with normal (≤2.0 mmol/L) versus elevated lactate (>2.0 mmol/L). Regression analyses examined associations of lactate measurements with ß2 -agonist dosages. RESULTS: Demographic data and comorbidities were similar between high versus normal lactate groups in both cohorts. The populations were elderly (mean >70 years), predominantly male (>60%) with reduced FEV1 (%) 48.2 ± 19 (prospective cohort). Lactate was elevated in approximately 50% of patients during AECOPD and not related to evidence of sepsis. In the prospective cohort, patients with high lactate had more tachypnoea, tachycardia, acidosis and hyperglycaemia (p < 0.05) and received more non-invasive ventilation (37% vs. 9.7%, p < 0.001, prospective cohort). There was a trend to longer hospitalization (6 vs. 5 days, p = 0.06, prospective cohort). Higher cumulative ß2 -agonist dosages were linked to elevated lactate levels (OR 1.04, p = 0.01). CONCLUSION: Elevated lactate during AECOPD was common, unrelated to sepsis and correlated with high cumulative doses of ß2 -agonists. Raised lactate may indicate excessive ß2 -agonist treatment and should now be investigated as a possible biomarker.

Computed Tomography Imaging of the Larynx for Diagnosis of Vocal Cord Dysfunction.

BACKGROUND: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO) is characterized by breathlessness and often mimics or accompanies severe asthma. The disorder occurs intermittently, and the diagnosis is established by using laryngoscopy. Dynamic computed tomography (CT) imaging of the larynx at low-radiation doses has the potential to provide an alternative method to make the diagnosis of VCD/ILO. METHODS: We report two case series: in series A, laryngoscopy (diagnostic standard) and CT imaging of the larynx were each performed within 1 hour of each other (n=31), and in series B, the procedures were performed on separate days 4 to 6 weeks apart (n=72). Diagnosis of VCD/ILO by laryngoscopy used conventional criteria, and diagnosis by CT imaging was based on vocal cord narrowing in excess of a validated normal threshold. In each series, we evaluated the accuracy of CT imaging of the larynx to establish a diagnosis of VCD/ILO compared with laryngoscopy. RESULTS: In series A, the sensitivity of CT imaging of the larynx was 53.8%, and specificity was 88.9%; in series B, the sensitivity of CT imaging of the larynx was 76.2%, and specificity was 93.3%. At a disease prevalence of 30% (which was known to be the case in our clinic), the positive predictive value was 67.5% in series A and 83% in series B. Negative predictive values were 81.8% and 90.1% in series A and B, respectively, and false-positive rates were 11.1% and 6.7%. CONCLUSIONS: When the population prevalence was assumed to be 30%, low-dose CT imaging of the larynx detected VCD/ILO with negative predictive values greater than 80% in both series settings and agreed with each other within 9 percentage points. Positive predictive values for laryngeal CT imaging varied substantially between the settings of the two case series. (Supported by Monash Lung and Sleep Institute and Grant APP ID 1198362 and others.)

Right ventricular end-diastolic volume and outcomes in exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Right ventricular (RV) volumes are crucial outcome determinants in pulmonary diseases. Little is known about the associations of RV volumes during hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We aimed to ascertain associations of RV end-diastolic volume indexed to body surface area (RVEDVI) during hospitalized AECOPD and its relationship with mortality in long-term follow-up. METHODS: This is a prospective observational cohort study (December 2013-November 2019, ACTRN12617001562369) using dynamic retrospective ECG-gated computed tomography during hospitalized AECOPD. RVEDVI was defined as normal or high using Framingham Offspring Cohort values. Cox regression determined the prognostic relevance of RVEDVI for death. RESULTS: A total of 148 participants (70 ± 10 years [mean ± SD], 88 [59%] men) were included, of whom 75 (51%) had high RVEDVI. This was associated with more frequent hospital admissions in the 12 months before admission (52/75 [69%] vs. 38/73 [52%], p = 0.04) and higher breathlessness (modified Medical Research Council score, 2.9 ± 1.3 vs. 2.4 ± 1.2, p = 0.007). During follow-up, high RVEDVI was associated with greater mortality (log-rank p = 0.001). In univariable Cox regression, increasing RVEDVI was associated with higher mortality (hazard ratio [HR]: 1.02 per ml/m2 ; 95% CI: 1.01, 1.03; p = 0.001). In multivariable Cox regression, RVEDVI was independently associated with mortality (HR: 1.01 per ml/m2 ; 95% CI: 1.00, 1.03; p = 0.050) at a borderline significance level. Adding RVEDVI to three COPD mortality prediction systems improved model fit (pooled chi-square test [BODE: p = 0.05, ADO: p = 0.04, DOSE: p = 0.02]). CONCLUSION: In patients with hospitalized AECOPD, higher RV end-diastolic volume was associated with worse acute clinical parameters and greater mortality.

Swallow patterns associated with aspiration in COPD: a prospective analysis.

Few studies have examined swallow of large liquid volumes representative of everyday drinking in COPD. Swallow by cup-drinking was evaluated in COPD using videofluoroscopy. Slower swallow was linked to aspiration indicating altered swallow habits in COPD. https://bit.ly/3wpdnO3.

MULTI-PHACET: multidimensional clinical phenotyping of hospitalised acute COPD exacerbations.

BACKGROUND: The generic term "exacerbation" does not reflect the heterogeneity of acute exacerbations of COPD (AECOPD). We utilised a novel algorithmic strategy to profile exacerbation phenotypes based on underlying aetiologies. METHODS: Patients hospitalised for AECOPD (n=146) were investigated for aetiological contributors summarised in a mnemonic acronym ABCDEFGX (A: airway virus; B: bacterial; C: co-infection; D: depression/anxiety; E: eosinophils; F: failure (cardiac); G: general environment; X: unknown). Results from clinical investigations were combined to construct AECOPD phenotypes. Relationships to clinical outcomes were examined for both composite phenotypes and their specific aetiological components. Aetiologies identified at exacerbation were reassessed at outpatient follow-up. RESULTS: Hospitalised AECOPDs were remarkably diverse, with 26 distinct phenotypes identified. Multiple aetiologies were common (70%) and unidentifiable aetiology rare (4.1%). If viruses were detected (29.5%), patients had longer hospitalisation (7.7±5.6 versus 6.0±3.9 days, p=0.03) despite fewer "frequent exacerbators" (9.3% versus 37%, p=0.001) and lower mortality at 1 year (p=0.03). If bacterial infection was found (40.4%), patients were commonly "frequent exacerbators" (44% versus 18.4%, p=0.001). Eosinophilic exacerbations (28%) were associated with lower pH (7.32±0.06 versus 7.36±0.09, p=0.04), higher venous carbon dioxide tension (P vCO2 ) (53.7±10.5 versus 48.8±12.8, p=0.04), greater noninvasive ventilation (NIV) usage (34.1% versus 18.1%) but shorter hospitalisation (4 (3-5) versus 6 (4-9) days, p<0.001) and lower infection rates (41.4% versus 80.9%, p<0.0001). Cardiac dysfunction and severe anxiety/depression were common in both infective and non-infective exacerbations. Characteristics identified at exacerbation often persisted after recovery. CONCLUSIONS: Hospitalised AECOPDs have numerous causes, often in combination, that converge in complex, multi-faceted phenotypes. Clinically important differences in outcomes suggest that a phenotyping strategy based on aetiologies can enhance AECOPD management.

Treatable cardiac disease in hospitalised COPD exacerbations.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) are accompanied by escalations in cardiac risk superimposed upon elevated baseline risk. Appropriate treatment for coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) could improve outcomes. However, securing these diagnoses during AECOPD is difficult, so their true prevalence remains unknown, as does the magnitude of this treatment opportunity. We aimed to determine the prevalence of severe CAD and severe HFrEF during hospitalised AECOPD using dynamic computed tomography (CT). METHODS: A cross-sectional study of 148 patients with hospitalised AECOPD was conducted. Dynamic CT was used to identify severe CAD (Agatston score ≥400) and HFrEF (left ventricular ejection fraction ≤40% and/or right ventricular ejection fraction ≤35%). RESULTS: Severe CAD was detected in 51 of 148 patients (35%), left ventricular systolic dysfunction was identified in 12 cases (8%) and right ventricular systolic dysfunction was present in 18 (12%). Clinical history and examination did not identify severe CAD in approximately one-third of cases and missed HFrEF in two-thirds of cases. Elevated troponin and brain natriuretic peptide did not differentiate subjects with severe CAD from nonsevere CAD, nor distinguish HFrEF from normal ejection fraction. Undertreatment was common. Of those with severe CAD, only 39% were prescribed an antiplatelet agent, and 53% received a statin. Of individuals with HFrEF, 50% or less received angiotensin blockers, beta blockers or antimineralocorticoids. CONCLUSION: Dynamic CT detects clinically covert CAD and HFrEF during AECOPD, identifying opportunities to improve outcomes via well-established cardiac treatments.

Aspiration and severe exacerbations in COPD: a prospective study.

RATIONALE: Swallow may be compromised in COPD leading to aspiration and adverse respiratory consequences. However, prevalence and consequences of detectable aspiration in stable COPD are not known. OBJECTIVES: We tested the hypothesis that a significant number of patients with stable COPD will have detectable aspiration during swallow (prandial aspiration) and that they would experience more frequent severe acute exacerbations of COPD (AECOPD) over the subsequent 12 months. METHODS: Patients (n=151) with verified and stable COPD of all severities were recruited at a tertiary care hospital. Videofluoroscopy was conducted to evaluate aspiration using Rosenbek's scale for penetration-aspiration during 100-mL cup drinking. AECOPD was documented as moderate (antibiotics and/or corticosteroid treatment) or severe (emergency department admission or hospitalisation) over the ensuing 12 months. MEASUREMENTS AND MAIN RESULTS: Aspiration was observed in 30 out of 151 patients (19.9%, 18 males, 12 females; mean age 72.4 years). Patients with aspiration had more overall AECOPD events (3.03 versus 2 per patient; p=0.022) and severe AECOPD episodes (0.87 versus 0.39; p=0.032). Severe AECOPD occurred in more patients with aspiration (50% of patients versus 18.2%; OR 4.5, CI 1.9-10.5; p=0.001) and with silent aspiration (36.7% versus 18.2%; OR 2.6, CI 1.1-6.2; p=0.045). Aspiration was related to a shorter exacerbation-free period during the 12-month follow-up period (p=0.038). CONCLUSIONS: Prandial aspiration is detectable in a subset of patients with COPD and was predictive of subsequent severe AECOPD. Studies to examine if the association is causal are essential to direct strategies aimed at prevention of aspiration and AECOPD.

Low and High Blood Eosinophil Counts as Biomarkers in Hospitalized Acute Exacerbations of COPD.

BACKGROUND: Characterizing acute exacerbations of COPD (AECOPD) and individualizing therapy is challenging. Key exacerbation therapies include antibiotics and systemic corticosteroids. Blood eosinophils, when either low or high, may offer a simple, inexpensive distinction to predict beneficial responses to these therapies. METHODS: We conducted derivation (n = 242) and validation (n = 99) cohort studies of patients hospitalized for AECOPD. Patients who received oral corticosteroids before ED presentation were excluded. The derivation cohort was identified by individual case file review. The validation cohort was prospectively recruited during hospital admission. Exacerbations were grouped according to blood eosinophil count as low (<50/µL), normal (50-150/µL), or high (>150/µL). Exacerbations were classified as being associated with infection if either virus testing was positive or C-reactive protein was ≥20 mg/L. Associations of eosinophil groups with infection, hospital length of stay, and 12-month survival were compared using appropriate statistical methods. RESULTS: There were no significant differences in baseline characteristics between patients with low, normal, or high blood eosinophils in either cohort. Eosinophil counts <50/µL were more strongly associated with infection (91% vs 51.9%, P = .001), distinguished patients with longer median hospital stays (7 vs 4 days, P < .001), and were associated with lower 12-month survival (82.4% vs 90.7%, P = .028; pooled data of both cohorts) than eosinophil counts >150/µL. CONCLUSIONS: Low and high blood eosinophil counts in hospitalized patients with AECOPD provide a practical clinical distinction that can potentially be used to inform management strategies. Prospective studies are needed to evaluate if this strategy can guide discriminate use of antibiotics and/or corticosteroids.

Multidisciplinary team clinic for vocal cord dysfunction directs therapy and significantly reduces healthcare utilization.

BACKGROUND AND OBJECTIVE: Multidisciplinary team (MDT) clinics use an integrated approach to individualize care of complex medical conditions. Vocal cord dysfunction (VCD) is a challenging condition that is likely to benefit from MDT clinics but this has not been researched. METHODS: A prospective observational cohort study of a novel VCD MDT clinic was conducted in patients with suspected VCD. Relevant questionnaires, medical history, physical examination, spirometry, dynamic computerized tomography (CT) larynx and laryngoscopy were utilized and patients were allocated to treatment pathways depending on putative diagnosis. Speech pathology intervention with laryngeal retraining (LR) was offered and if LR therapy failed botulinum toxin injection was offered. Primary outcome was reductions in healthcare utilization. RESULTS: Overall, 80 consecutive patients were included in analyses. A definitive diagnosis of VCD was made in 56 of 80 (70%) patients. After LR (n = 35), emergency department (ED)/hospital admissions declined significantly in the subsequent 12 months (P = 0.001). General practice visits also reduced (P < 0.001). Botulinum toxin injections were administered in 21 patients unresponsive to LR therapy and both general practice and ED/hospital visits declined (P < 0.001 and P = 0.01, respectively) after injection. CONCLUSION: A multidisciplinary approach to VCD confers benefit and can be used to allocate appropriate management leading to a reduction in healthcare utilization.

Dysfunctional breathing is more frequent in chronic obstructive pulmonary disease than in asthma and in health.

Involuntary adaptations of breathing patterns to counter breathlessness may lead to dysfunctional breathing in obstructive lung diseases. However, no studies examining dysfunctional breathing in Chronic Obstructive Pulmonary Disease (COPD) have been reported. Patients with verified COPD (n=34), asthma (n=37) and a healthy control group (n=41) were recruited. All participants completed the Nijmegen questionnaire for dysfunctional breathing as well as measures of disease activity. Comparisons between groups employed analysis of variance with post-hoc Bonferroni analyses and Pearson correlation for associations. Patients with COPD had significantly higher Nijmegen questionnaire scores than asthmatics (COPD: 23.4±10.6 versus 17.3±10.6, p=0.016) and healthy individuals (14.3±9.6, p=0.002). Significantly more patients with COPD had severe dysfunctional breathing with Nijmegen scores >23 (47%; 16/34) compared to asthma (27%; 10/37) and healthy controls (17%; 7/41) respectively (p=0.019). Dysfunctional breathing was detected in ∼50% of patients with COPD, more so than in asthma or health. Strategies to reduce abnormal breathing behaviours may have important benefits for treatment of breathlessness in COPD.

On the establishment, persistence, and inevitable extinction of populations.

Comprehensive models of stochastic, clonally reproducing populations are defined in terms of general branching processes, allowing birth during maternal life, as for higher organisms, or by splitting, as in cell division. The populations are assumed to start small, by mutation or immigration, reproduce supercritically while smaller than the habitat carrying capacity but subcritically above it. Such populations establish themselves with a probability wellknown from branching process theory. Once established, they grow up to a band around the carrying capacity in a time that is logarithmic in the latter, assumed large. There they prevail during a time period whose duration is exponential in the carrying capacity. Even populations whose life style is sustainble in the sense that the habitat carrying capacity is not eroded but remains the same, ultimately enter an extinction phase, which again lasts for a time logarithmic in the carrying capacity. However, if the habitat can carry a population which is large, say millions of individuals, and it manages to avoid early extinction, time in generations to extinction will be exorbitantly long, and during it, population composition over ages, types, lineage etc. will have time to stabilise. This paper aims at an exhaustive description of the life cycle of such populations, from inception to extinction, extending and overviewing earlier results. We shall also say some words on persistence times of populations with smaller carrying capacities and short life cycles, where the population may indeed be in danger in spite of not eroding its environment.

Evaluation of the role of lung volume and airway size and shape in supine-predominant obstructive sleep apnoea patients.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the involvement of airway cross-sectional area and shape, and functional residual capacity (FRC), in the genesis of obstructive sleep apnoea (OSA) in patients with supine-predominant OSA. METHODS: Three groups were recruited: (i) supine OSA, defined as a supine apnoea-hyponoea index (AHI) at least twice that of the non-supine AHI; (ii) rapid eye movement (REM) OSA, defined as REM AHI at least twice the non-REM AHI and also selected to have supine AHI less than twice that of the non-supine AHI (i.e. to be non-positional); and (iii) no OSA, defined as an AHI less than five events per hour. The groups were matched for age, gender and body mass index. Patients underwent four-dimensional computed tomography scanning of the upper airway in the supine and lateral decubitus positions. FRC was measured in the seated, supine and lateral decubitus positions. RESULTS: Patients with supine OSA demonstrated a significant decrease in FRC of 340 mL (P = 0.026) when moving from the lateral to supine position compared to controls with no OSA, and REM OSA patients. We found no differences between groups in upper airway size and shape. However, all groups showed a significant change in airway shape with the velopharyngeal airway adopting a more elliptoid shape (with the long axis laterally oriented), with reduced anteroposterior diameter in the supine position. CONCLUSIONS: A fall in FRC when moving lateral to supine in supine OSA patients may be an important triggering factor in the generation of OSA in this patient group.

A mathematical model for eph/ephrin-directed segregation of intermingled cells.

Eph receptors, the largest family of receptor tyrosine kinases, control cell-cell adhesion/de-adhesion, cell morphology and cell positioning through interaction with cell surface ephrin ligands. Bi-directional signalling from the Eph and ephrin complexes on interacting cells have a significant role in controlling normal tissue development and oncogenic tissue patterning. Eph-mediated tissue patterning is based on the fine-tuned balance of adhesion and de-adhesion reactions between distinct Eph- and ephrin-expressing cell populations, and adhesion within like populations (expressing either Eph or ephrin). Here we develop a stochastic, Lagrangian model that is based on Eph/ephrin biology: incorporating independent Brownian motion to describe cell movement and a deterministic term (the drift term) to represent repulsive and adhesive interactions between neighbouring cells. Comparison between the experimental and computer simulated Eph/ephrin cell patterning events shows that the model recapitulates the dynamics of cell-cell segregation and cell cluster formation. Moreover, by modulating the term for Eph/ephrin-mediated repulsion, the model can be tuned to match the actual behaviour of cells with different levels of Eph expression or activity. Together the results of our experiments and modelling suggest that the complexity of Eph/ephrin signalling mechanisms that control cell-cell interactions can be described well by a mathematical model with a single term balancing adhesion and de-adhesion between interacting cells. This model allows reliable prediction of Eph/ephrin-dependent control of cell patterning behaviour.

Night-to-night repeatability of supine-related obstructive sleep apnea.

RATIONALE: Patients with obstructive sleep apnea (OSA) experience respiratory events with greater frequency and severity while in the supine sleeping position. Postural modification devices (PMDs) prevent supine sleep, although there is a paucity of guidance to help clinicians decide when to use PMDs for their patients. In order for PMDs to treat OSA effectively, patients must experience respiratory events in the supine sleeping position consistently from night to night and must have a low nonsupine apnea and hypopnea index (AHINS). OBJECTIVES: To document the repeatability of traditionally defined supine predominant OSA on consecutive polysomnography, to determine whether the consistency of the supine-predominant phenotype can be improved by altering the definition of it, and to determine whether a low AHINS is repeatable from night to night. METHODS: We recruited 75 patients for polysomnography on two separate nights. Patients were classified as having supine OSA on each night on the basis of traditional and novel definitions, and the classification systems used were compared on the basis of agreement from night to night. MEASUREMENTS AND MAIN RESULTS: The definition of supine OSA with the highest level of agreement from night to night incorporates a supine AHI (AHIS) to AHINS ratio ≥4:1. In addition, agreement exists for males, but there is poor agreement for female patients, regardless of the definition applied. An AHINS <10 events/hour is highly repeatable from night to night. CONCLUSIONS: Males with an AHIS:AHINS ratio ≥4:1 and an AHINS <10 events/hour represent a consistent supine-predominant OSA phenotype from night to night. This patient group is likely to benefit from treatment with PMD.

Abnormal vocal cord movement treated with botulinum toxin in patients with asthma resistant to optimised management.

BACKGROUND AND OBJECTIVE: Abnormal vocal cord movement may coexist with asthma and cause additional upper/middle airway obstruction. The condition may be a form of muscular dystonia that could contribute to asthma resistant to optimised treatments. Botulinum toxin causes temporary paralysis of muscle and may be an effective local treatment that improves asthma control. METHODS: In an observational study, we evaluated the benefits of unilateral vocal cord injection with botulinum toxin in 11 patients (total 24 injections). Subjects had asthma resistant to optimised treatment and abnormal vocal cord movement. Responses after botulinum toxin treatment were assessed using asthma control test (ACT) scores, vocal cord narrowing quantified by computerised tomography (CT) of the larynx and spirometry. Side-effects were recorded. RESULTS: ACT scores improved overall (9.1 ± 2.4 before and 13.5 ± 4.5 after treatment; difference 4.4 ± 4.2; P < 0.001). There was also an improvement in airway size on CT larynx (time below lower limit of normal at baseline 39.4 ± 37.63% and improved to 17.6 ± 25.6% after injection; P = 0.032). Spirometry was not altered. One patient experienced an asthma exacerbation but overall side-effects were moderate, chiefly dysphonia and dysphagia. CONCLUSIONS: Although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.

Lung-volume controlled computerised tomography in real-life acute severe asthma.

OBJECTIVE: It is not known how airway structure is altered during real-life acute asthma exacerbations. The aim of this study was to examine changes in airway structure during acute asthma exacerbations and at convalescence by using lung-volume controlled high resolution computerised tomography (HRCT). METHODS: Eight subjects with acute asthma exacerbation admitted to hospital were recruited. HRCT was performed within 72 h of admission (n = 8) and repeated after 8 weeks of convalescence (n = 7). Individual airways were carefully matched on acute and convalescent CT data sets for comparisons of airway parameters. A novel methodology was employed for standardisation of lung volumes to permit valid comparisons of lung imaging. Measurements of bronchial cross sectional airway area (Aa) and bronchial luminal area (Ai) for each matched airway were obtained using a validated program. RESULTS: The airway wall thickness was analysed as wall area (WA) calculated as a percentage: WA% = WA/Aa × 100. Wilcoxon signed-rank testing was used to compare acute and convalescent asthma and Spearman's correlation to examine associations. Airway lumen (Ai) areas were similar in both acute and stable asthma phases (6.6 ± 3.1 mm(2) versus 7.2 ± 3.8 mm(2) p = 0.8). However, the airway wall was significantly thickened during acute asthma exacerbations compared to convalescence (62 ± 4% versus 55 ± 7%; p = 0.01). There was no correlation between airway structure dimensions and lung function measurements. CONCLUSIONS: This is the first study to demonstrate an increase in airway wall thickness during real-life acute asthma exacerbation. However, narrowing of the airway lumen area was variable and will require larger studies able to detect small differences. These results suggest that airway wall thickening linked to mucosal inflammation is likely to characterise acute asthma in vivo but that changes in the airway lumen accompanying bronchoconstriction may be more heterogeneous.

Exacerbation phenotyping in chronic obstructive pulmonary disease.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are crucial events but causes remain poorly defined. A method to clinically 'phenotype' AECOPD have been proposed, and 52 hospitalized chronic obstructive pulmonary disease exacerbations according to underlying aetiology have now been prospectively phenotyped. Multiple exacerbation phenotypes were identified. A subpopulation coinfected with virus and bacteria had a significantly longer length of hospital stay, and this pilot study indicates that exacerbation phenotyping may be advantageous.