Cough hypersensitivity and suppression in COPD.

Cough reflex hypersensitivity and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and cough reflex hypersensitivity in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of patients with COPD to suppress cough during a cough challenge test in comparison to patients with CRC and healthy subjects. This study also investigated whether cough reflex hypersensitivity is associated with chronic cough in COPD.Participants with COPD (n=27) and CRC (n=11) and healthy subjects (n=13) underwent capsaicin challenge tests with and without attempts to self-suppress cough in a randomised order over two visits, 5 days apart. For patients with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured.Amongst patients with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity compared to those without chronic cough (n=11): geometric mean±sd capsaicin dose thresholds for five coughs (C5) 3.36±6.88 µmol·L-1 versus 44.50±5.90 µmol·L-1, respectively (p=0.003). Participants with CRC also had heightened cough reflex sensitivity compared to healthy participants: geometric mean±sd C5 3.86±5.13 µmol·L-1 versus 45.89±3.95 µmol·L-1, respectively (p<0.001). Participants with COPD were able to suppress capsaicin-evoked cough, regardless of the presence or absence of chronic cough: geometric mean±sd capsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36±6.88 µmol·L-1 versus 12.80±8.33 µmol·L-1 (p<0.001) and 44.50±5.90 µmol·L-1 versus 183.2±6.37 µmol·L-1 (p=0.006), respectively. This was also the case for healthy participants (C5 versus CS5: 45.89±3.95 µmol·L-1 versus 254.40±3.78 µmol·L-1, p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5 versus CS5: 3.86±5.13 µmol·L-1 versus 3.34±5.04 µmol·L-1, p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in patients with COPD: ρ= -0.430, p=0.036 and ρ= -0.420, p=0.041, respectively.Patients with COPD-chronic cough and CRC both had heightened cough reflex sensitivity but only patients with CRC were unable to suppress capsaicin-evoked cough. This suggests differing mechanisms of cough between patients with COPD and CRC, and the need for disease-specific approaches to its management.

The Relationship Between Cough Reflex Sensitivity and Exacerbation Frequency in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Cough is predictive of exacerbations of chronic obstructive pulmonary disease (COPD). Little is known about cough reflex sensitivity during exacerbation of COPD and whether it is associated with exacerbation frequency. This pilot study aimed to investigate cough reflex sensitivity during and following recovery from exacerbation of COPD, and its association with the frequency of future exacerbations. In addition, the repeatability of cough reflex sensitivity in stable COPD was investigated. METHODS: Twenty participants hospitalised with exacerbation of COPD underwent inhaled capsaicin challenge during exacerbation and after 6 weeks of recovery. The frequency of future exacerbations was monitored for 12 months. The repeatability of cough reflex sensitivity was assessed in separate participants with stable COPD, who underwent 2 capsaicin challenge tests, 6 weeks apart. RESULTS: Cough reflex sensitivity was heightened during exacerbation of COPD. Geometric mean (SD) capsaicin concentration thresholds to elicit 5 coughs (C5) during exacerbation and after 6 weeks of recovery were 1.76 (3.73) vs. 8.09 (6.25) µmol L-1, respectively (p < 0.001). The change in C5 from exacerbation to 6-week recovery was associated with the frequency of future exacerbations (ρ = - 0.687, p = 0.003). C5 was highly repeatable over 6 weeks in stable COPD, and intraclass correlation coefficient was 0.85. CONCLUSION: Cough reflex sensitivity is heightened during exacerbation of COPD and reduces after recovery. The persistence of cough reflex hypersensitivity at recovery was associated with the frequency of future exacerbations.

A centralised respiratory diagnostic service for primary care: a 4-year audit.

BACKGROUND: The literature shows that delayed or erroneous diagnosis of respiratory conditions may be common in primary care due to underuse of spirometry or poor spirometric technique. The Community Respiratory Assessment Unit (CRAU) was established to optimise diagnosis and treatment of respiratory disease by providing focused history-taking, quality-assured spirometry, and evidence-based guideline-derived management advice. AIMS: To review the service provided by the CRAU to primary care health professionals. METHODS: Data from 1,156 consecutive GP referrals over 4 years were analysed. RESULTS: From the 1,156 referrals, 666 were referred for one of five common reasons: suspected asthma, confirmed asthma, suspected chronic obstructive pulmonary disease (COPD), confirmed COPD, or unexplained breathlessness. COPD was the most prevalent referral indication (445/666, 66.8%), but one-third of suggested diagnoses of COPD by the GP were found to be incorrect (161/445, 36%) with inappropriate prescribing of inhaled therapies resulting from this misdiagnosis. Restrictive pulmonary defects (56/666, 8% of referrals) were overlooked and often mistaken for obstructive conditions. The potential for obesity to cause breathlessness may not be fully appreciated. CONCLUSIONS: Misdiagnosis has significant financial, ethical, and safety implications. This risk may be minimised by better support for primary care physicians such as diagnostic centres (CRAU) or alternative peripatetic practice-based services operating to quality-controlled standards.

Airway and systemic inflammation and decline in lung function in patients with COPD.

STUDY OBJECTIVES: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1. PATIENTS AND DESIGN: A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8). At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3). RESULTS: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 x 10(6) cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05). Patients with frequent exacerbations (> or = 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively. CONCLUSIONS: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.

Airway and systemic inflammation and decline in lung function in patients with COPD

Study objective: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline FEV. Patient and design: a cohort of 148 COPD patients (100 men) was monitored daily for a median 2.9 years (interquartile range [IQR], 2.1 to 4.8). At recruitment median age was 68.5 years (IQR, 62.5 to 73.6) and FEV as percentage of predicted (FEV percent Pred) was 38.5 percent (IQR, 27.7 to 50.3). Results: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR 1.48 to 3.96) and FEV declined by 40.2 mL/yr or as FEV percent Pred by 1.5 percent/yr. Concerning inflammatory markers, sputum interlukin (IL)-6 rose by 9 pg/mL, sputum neutrophil count rose by 1.64 x 10,000,000 cells per gram sputum per year, and plasma fibrinogen rose by 0.10 g/L/yr (all p, 0.05). Patients with frequent exacerbations (less than or equal to 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p= 0.046, n= 130) and 29.5 pg/mL/yr (p< 0.001, n=98), respectively, compared to patients with infrequent exacerbations (<2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV percentPred decline of 0.97 percent/yr (p=0.001 and .40 percent/yr (p=0.014). respectively. Conclusions: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function (AU)

Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease.

Relationships between high-resolution computed tomography (HRCT) findings in chronic obstructive pulmonary disease (COPD) and bacterial colonization, airway inflammation, or exacerbation indices are unknown. Fifty-four patients with COPD (mean [SD]: age, 69 [7] years; FEV(1), 0.96 [0.33] L; FEV(1) [percent predicted], 38.1 [13.9]%; FEV(1)/forced vital capacity [percent predicted], 40.9 [11.8]%; arterial partial pressure of oxygen, 8.77 [1.11] kPa; history of smoking, 50.5 [33.5] smoking pack-years) underwent HRCT scans of the chest to quantify the presence and extent of bronchiectasis or emphysema. Exacerbation indices were determined from diary cards over 2 years. Quantitative sputum bacteriology and cytokine measurements were performed. Twenty-seven of 54 patients (50%) had bronchiectasis on HRCT, most frequently in the lower lobes (18 of 54, 33.3%). Patients with bronchiectasis had higher levels of airway inflammatory cytokines (p = 0.001). Lower lobe bronchiectasis was associated with lower airway bacterial colonization (p = 0.004), higher sputum interleukin-8 levels (p = 0.001), and longer symptom recovery time at exacerbation (p = 0.001). No relationship was seen between exacerbation frequency and HRCT changes. Evidence of moderate lower lobe bronchiectasis on HRCT is common in COPD and is associated with more severe COPD exacerbations, lower airway bacterial colonization, and increased sputum inflammatory markers.

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.

Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function and progressive airway inflammation. Bacteria have been isolated from the lower airway of stable COPD patients, and airway inflammation has been related to bacterial load and type. The relationship between bacterial colonization, airway inflammation, and lung function decline remains uncertain. We studied 30 patients with COPD, mean (SD) FEV1 0.947 (0.329), 34.8% (13.6%) predicted, for 12 months. Sputum collected at recruitment and the end of the study was analyzed for cytokines and for quantitative bacteriology. The decline in FEV1 was 57.6 (137.6) ml year-1. Bacterial growth was identified in all subjects, with an initial count of 107.47(0.91) cfu ml-1 rising to 107.93(0.81) cfu ml-1 at the end of the study (p = 0.019). FEV1 decline was related to this increase in airway bacterial load (r = 0.59, p = 0.001). FEV1 decline was greater in subjects who exhibited a change in the colonizing bacterial type compared with those with persistence of a single bacterial species over the study period (p = 0.017). Higher sputum interleukin (IL-8) was associated with greater declines in FEV1 (p = 0.03). Rising airway bacterial load and species changes are associated with greater airway inflammation and accelerated decline in FEV1. Bacterial colonization in COPD is an important factor in disease progression.