Gavin C. Donaldson

Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations. The aim of this study was to investigate whether these are related. Methods: Over 4 years, peak expiratory flow (PEF) and symptoms were measured at home daily by 109 patients with COPD (81 men; median (IQR) age 68.1 (63–74) years; arterial oxygen tension (Pao2) 9.00 (8.3–9.5) kPa, forced expiratory volume in 1 second (FEV1) 1.00 (0.7–1.3) l, forced vital capacity (FVC) 2.51 (1.9–3.0) l); of these, 32 (29 men) recorded daily FEV1. Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations (> or < 2.92 per year) on lung function decline was examined using cross sectional, random effects models. Results: The 109 patients experienced 757 exacerbations. Patients with frequent exacerbations had a significantly faster decline in FEV1 and peak expiratory flow (PEF) of –40.1 ml/year (n=16) and –2.9 l/min/year (n=46) than infrequent exacerbators in whom FEV1 changed by –32.1 ml/year (n=16) and PEF by –0.7 l/min/year (n=63). Frequent exacerbators also had a greater decline in FEV1 if allowance was made for smoking status. Patients with frequent exacerbations were more often admitted to hospital with longer length of stay. Frequent exacerbations were a consistent feature within a patient, with their number positively correlated (between years 1 and 2, 2 and 3, 3 and 4). Conclusions: These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD.

Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD.

n n Study objectivesn The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.n n n Designn Prospective cohort study.n n n Settingn Outpatient Department, London Chest Hospital, London, UK.n n n Patientsn Thirty-nine patients with COPD.n n n Measurementsn We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.n n n Resultsn A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.n n n Conclusionsn The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.n n

Relationships Among Bacteria, Upper Airway, Lower Airway, and Systemic Inflammation in COPD

STUDY OBJECTIVEnThe upper and lower airways are continuous. While upper airway symptoms are common in COPD patients, with accumulating evidence to suggest increased nasal inflammation, the relationships among upper airway, lower airway, and systemic inflammatory indexes have not been studied. We aimed to confirm that there is heightened nasal inflammation in COPD patients, to test the hypothesis that the degree of upper airway inflammation relates to the degree of lower airway inflammation, and to investigate the underlying associations with bacterial carriage and the systemic inflammatory response.nnnDESIGNnProspective cohort study.nnnSETTINGnOutpatient Department, London Chest Hospital, London, UK.nnnPARTICIPANTSnForty-seven patients with COPD and 12 control subjects of similar age, sex, and smoking status.nnnMEASUREMENTSnSerum, nasal wash fluid, and sputum samples were obtained from 47 stable patients with COPD for the analysis of inflammatory indexes and bacterial colonization. Nasal wash fluid specimens were obtained from 12 control subjects.nnnRESULTSnCOPD patients had an increased nasal interleukin (IL)-8 concentration compared to control subjects (difference, 97.2 pg/mL; p = 0.009). The nasal IL-8 concentration in COPD patients correlated with that in sputum (r = 0.30; p = 0.039). In both the upper and lower airways of patients with COPD, the IL-8 concentration was associated with indexes of bacterial colonization. Patients colonized with a sputum potentially pathogenic microorganism had a higher total nasal bacterial load (difference, 1.5 log cfu/mL; p = 0.016). We did not find significant relationships between the degree of upper or lower airway inflammation, or bacterial carriage, and the systemic inflammatory response.nnnCONCLUSIONSnCOPD is associated with an increased nasal concentration of the neutrophil chemoattractant protein IL-8, the degree of which reflects that present in the lower airway. A relationship between lower airway bacterial colonization, postnasal drip, and higher nasal bacterial load may suggest a mechanism underlying this finding. This study is the first to report a correlation between the degree of upper and lower airway inflammation in COPD.

Relationship between chronic nasal and respiratory symptoms in patients with COPD

The relationship between the upper and lower airways in chronic obstructive pulmonary disease (COPD) is unknown. We examined the prevalence of chronic nasal symptoms and the correlation with lower respiratory symptoms and parameters of severity of COPD such as exacerbation frequency and spirometry. 61 COPD patients from the East London COPD cohort were studied. [Mean (SD) age 70 (6.96) years, FEV1 0.98 (0.38) l, FVC 2.45 (0.72) l, FEV1%Pred 37.0 (12.3), and 47.6 (31.8) smoking pack years, 14 current smokers, 36 males]. COPD patients had a high prevalence of nasal symptoms (75%), more than half reporting nasal discharge (52.5%) and sneezing (45.9%). Associations were found between nasal score and daily sputum production (P = 0.005) and post-nasal drip and sputum production (P = 0.046) with a trend to increased nasal symptoms in frequent exacerbators compared to infrequent exacerbators. No significant relationship was found between nasal symptoms and FEV1 or any other lower respiratory airway symptom. Associations between nasal and respiratory symptoms were found suggesting that there is a relationship between the upper and lower airway in COPD.

Mechanisms of cold intolerances in patients with angina

Abstract Objectives. Patients with angina often report that symptoms are worse in cold weather, This study was designed to determine differences between cold-tolerant and cold-intolerant patients in the hemodynamic and ichemic response to exercise at cold temperature and to assess the role of catechlomines and baroreceptor function. Background. Studies have suggested that the heart rate response may differ at cold temperatures, but the mechanism and role of this variation have not been examined. Methods. Seven cold-intolerant and seven cold-tolerant patients with angina underwent exercise treadmill testing at 6 and 25 °C wtth measurement of catecholamines. Baroreceptor function was assessed by the decrease in systolic blood pressure after patients stood up from the supine position. Results. Norepinephrine levels increased by 139% in the cold environment, but there were no differences between cold-intolerant and cold-tolerant patients. Consequently, blood pressure was higher in the cold environment in all patients, but the heart rate was similar. However, cold-intolerant patients had a steeper heart rate response in the cold and developed ischemia (mean [±SEM] 201 ± 58 vs. 242 ± 50 s, p = 0.05) and (348 ± 87 vs. 449 ± 60 s, p = 0.04) earlier in the cold environment, a difference not seen in the cold-tolerant patients Baroreceptor function was impaired in cold-intolerant patients. (decrease in systolic blood presure after patients stood up from the supine position 19 ± 7 vs. 0 ± 4 mm Hg, p = 0.04). Conclusions. Exposure to cold causes an increase in blood pressure with an associated increase in myocardial oxygen demand in all patients. In cold-tolerant patients, this increase may be offset by a reduction in heart rate if baroreceptor function is normal. If baroceptor function is abnormal, heart rate may not decrease in response to a cold-induced increased in pressure. This mechanisms may account for some of the variability in tolerance to cold exposure that affects patients with exertional angina.

Winter mortality in elderly people in Britain: Action on outdoor cold stress is needed to reduce winter mortality

EDITOR—The paper by Wilkinson et al, on people aged over 75, makes a useful addition to the evidence that winter mortality in Britain is now not caused primarily by deprivation and failure to heat homes.1 In addition to other evidence they quote, a recent study on younger people provides positive indications that cold exposure outside the home causes winter mortality regardless …

Effect of posture on body temperature of young men in cold air.

We studied eight young adult men to see whether a supine posture caused a fall in body core temperature in the cold, as it does in thermoneutral conditions. In air at 31°C (thermoneutral), a supine posture for 3 h reduced mean aural, gastric, oesophageal and rectal temperatures by 0.2–0.4°C, compared to upright and increased femoral artery blood flow from 278 (SEM 42) ml · min−1 whilst upright to 437 (SEM 42) ml·min−1 whilst supine. In cold air (8°C) the supine posture failed to reduce these temperature differences significantly, or to increase femoral blood flow; it reduced heart rate, and increased arterial systolic and pulse pressures adjusted to carotid sinus level, less than in thermoneutral conditions. However, the behaviour of core temperature at the four sites was significantly nonuniform between the two postures in the cold, mainly because the supine posture tended to reduce rectal temperature. It may have done so by reducing heat production in the muscles of the pelvis, since it reduced overall metabolic rate from 105 (SEM 8) to 87 (SEM 4) W · m−2 in the cold. In other respects the results indicated that posture ceased to have an important effect on body core temperatures during cold stress.