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Biomedical subjects

G C Donaldson

Publications and source records attributed to G C Donaldson.

At least 19 recordsLinked to original sources
PubMed2006

Inflammatory changes, recovery and recurrence at COPD exacerbation.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days. Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35 days post-exacerbation. In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8 mg.L(-1) versus 3.4 mg.L(-1). Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators. Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.

Administration, Inhalation↗
PubMed2006

COPD exacerbations .1: Epidemiology.

The epidemiology of exacerbations of chronic obstructive pulmonary disease (COPD) is reviewed with particular reference to the definition, frequency, time course, natural history and seasonality, and their relationship with decline in lung function, disease severity and mortality. The importance of distinguishing between recurrent and relapsed exacerbations is discussed.

Adult↗
PubMed2005

MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation.

BACKGROUND: Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood. This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation. METHODS: Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to 1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand. RESULTS: MMP-9 levels increased from 10.5 microg/g [1.2 to 21.1] prior to exacerbation to 17.1 microg/g [9.3 to 48.7] during exacerbation (P < 0.01). TIMP-1 levels decreased from 3.5 microg/g [0.6 to 7.8] to 1.5 microg/g [0.3 to 4.9] (P = 0.16). MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05). Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05). Macrophage numbers remained level. MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01). CONCLUSION: During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline.

Aged↗
PubMed2005

Changes in mortalities and hospital admissions associated with holidays and respiratory illness: implications for medical services.

RATIONALE AND OBJECTIVES: To see whether net mortalities increase during and after reductions in medical services, either at average weekends, or at Christmas when pressure from illness is unusually high. METHODS: (1) Paired t-tests to compare mean daily deaths and hospital admissions during and after weekends (Saturday-Tuesday) with means for the week, in south-east England; (2) Linear regressions to see whether trends of daily deaths change when admissions are reduced at Christmas. RESULTS: Neither mean daily all-cause, respiratory or ischaemic heart deaths exceeded weekly averages during weekends, or during Saturday-Monday or Saturday-Tuesday, despite falls in daily elective and daily emergency hospital admissions at weekends that averaged 61-72% and 14-22%, respectively. During 19-24 December, daily deaths were above annual means, respiratory deaths by 49% (29, 1-58), but elective admissions fell and although emergency admissions tended to rise, total admissions rose only for respiratory disease, and only by 33% (376, -47 to 799). On Christmas Day (25 December), even emergency admissions fell sharply below previous trends, respiratory emergency admissions by 18% (P<0.01). Respiratory deaths alone then immediately increased (P<0.01) above trend, by 5.9% (5.8 deaths/day) on 26 December and by 12.9% (12.9) on 27 December. CONCLUSIONS: No adverse effect on mortality was apparent within 2 days from reduction in medical services at weekends. However, respiratory deaths accelerated sharply after reduction in elective and emergency admissions at Christmas, when rates of infection and mortality from respiratory disease were high. Implications for medical services during respiratory epidemics are discussed.

Cause of Death↗
PubMed2005

Epidemiological relationships between the common cold and exacerbation frequency in COPD.

Higher exacerbation incidence rates in chronic obstructive pulmonary disease (COPD) are associated with more rapid decline in lung function and poorer quality of life, yet the mechanisms determining susceptibility to exacerbation remain ill-defined. The same viruses responsible for common colds are frequently isolated during exacerbations. The current authors hypothesised that exacerbation frequency may be associated with an increased frequency of colds, and investigated whether increased exacerbation frequency was associated with increased acquisition of colds, or a greater likelihood of exacerbation once a cold has been acquired. A total of 150 patients with COPD completed diary cards recording peak expiratory flow, and respiratory and coryzal symptoms for a median 1,047 days. Annual cold and exacerbation incidence rates (cold and exacerbation frequency) were calculated, and the relationships between these variables were investigated. This analysis is based on 1,005 colds and 1,493 exacerbations. Frequent exacerbators (i.e. those whose exacerbation frequency was greater than the median) experienced significantly more colds than infrequent exacerbators (1.73 versus 0.94.yr(-1)). The likelihood of exacerbation during a cold was unaffected by exacerbation frequency. Patients experiencing frequent colds had a significantly higher exposure to cigarette smoke (46 versus 33 pack-yrs). Exacerbation frequency in chronic obstructive pulmonary disease is associated with an increased frequency of acquiring the common cold, rather than an increased propensity to exacerbation once a cold has been acquired.

Aged↗
PubMed2005

Effects of exacerbations and seasonality on exhaled nitric oxide in COPD.

Exhaled nitric oxide (eNO) appears to be associated with airway inflammation seen in chronic obstructive pulmonary disease (COPD). The present authors studied the effects of exacerbation, season, temperature and pollution on eNO. eNO was measured seasonally and at exacerbations in 79 outpatients suffering from COPD (mean forced expiratory volume in one second=42%). The effects of exacerbation symptoms, physiological and environmental parameters were analysed. Stable eNO levels were correlated positively with arterial oxygen tension. Median levels were found to be lower in smokers (5.3 ppb) than in ex- or nonsmokers (6.8 ppb). Levels were higher during October to December (6.9 ppb) than in April to June (4.6 ppb). Levels were also higher during 68 exacerbations in 38 patients (7.4 ppb) than in stable conditions (5.4 ppb), independent of the effects of smoking. The rise in eNO was greater in exacerbations that were associated with colds, a sore throat or dyspnoea combined with a cold. In conclusion, exhaled nitric oxide levels were higher in colder weather and in the autumn, perhaps related to the increased prevalence of viral infection at this time of year. The levels were lower in more severe chronic obstructive pulmonary disease. Exhaled nitric oxide levels were raised at the onset of exacerbation, particularly in the presence of a cold.

Age Distribution↗
PubMed2005

Patterns of home mechanical ventilation use in Europe: results from the Eurovent survey.

The study was designed to assess the patterns of use of home mechanical ventilation (HMV) for patients with chronic respiratory failure across Europe. A detailed questionnaire of centre details, HMV user characteristics and equipment choices was sent to carefully identified HMV centres in 16 European countries. A total of 483 centres treating 27,118 HMV users were identified. Of these, 329 centres completed surveys between July 2001 and June 2002, representing up to 21,526 HMV users and a response rate of between 62% and 79%. The estimated prevalence of HMV in Europe was 6.6 per 100,000 people. The variation in prevalence between countries was only partially related to the median year of starting HMV services. In addition, there were marked differences between countries in the relative proportions of lung and neuromuscular patients using HMV, and the use of tracheostomies in lung and neuromuscular HMV users. Lung users were linked to a HMV duration of <1 yr, thoracic cage users with 6-10 yrs of ventilation and neuromuscular users with a duration of > or =6 yrs. In conclusion, wide variations exist in the patterns of home mechanical ventilation provision throughout Europe. Further work is needed to monitor its use and ensure equality of provision and access.

Adolescent↗
PubMed2004

The impact of global warming on health and mortality.

Initial concern about the possible effects of global warming on infections has declined with the realization that the spread of tropical diseases is likely to be limited and controllable. However, the direct effects of heat already cause substantial numbers of deaths among vulnerable people in the summer. Action to prevent these deaths from rising is the most obvious medical challenge presented by a global rise in temperature. Strategies to prevent such deaths are in place to some extent, and they differ between the United States and Europe. Air conditioning has reduced them in the United States, and older technologies such as fans, shade, and buildings designed to keep cool on hot days have generally done so in Europe. Since the energy requirements of air conditioning accelerate global warming, a combination of the older methods, backed up by use of air conditioning when necessary, can provide the ideal solution. Despite the availability of these technologies, occasional record high temperatures still cause sharp rises in heat-related deaths as the climate warms. The most important single piece of advice at the time a heat wave strikes is that people having dangerous heat stress need immediate cooling, eg, by a cool bath. Such action at home can be more effective than transporting the patient to hospital. Meanwhile, it must not be forgotten that cold weather in winter causes-many more deaths than heat in summer, even in most subtropical regions, and measures to control cold-related deaths need to continue.

Aged↗
PubMed2003

Changes in summer temperature and heat-related mortality since 1971 in North Carolina, South Finland, and Southeast England.

Three climatically diverse regions were studied to determine the impact of temperature change on heat-related mortality from 1971 to 1997. Median regressions showed that May-August temperatures in North Carolina rose by 1.0 degrees C (95% CL 0.0-2.0 degrees C) from 23.5 degrees C (74.3 degrees F), were unchanged in South Finland at 13.5 degrees C (56.3 degrees F), and rose in Southeast England 2.1 degrees C (0.3-4.0 degrees C) from 14.9 degrees C (58.8 degrees F). After determining for each region the daily temperature (as a 3 degrees C band) at which the mortality was the lowest, annual heat-related mortality was obtained as excess mortality per million at temperatures above this. Annual heat-related mortality per million (among the population at risk, aged 55+) fell in North Carolina by 212 (59-365) from 228 (140-317) to only 16 (not significant, NS); fell in South Finland by 282 (66-500) from 382 (257-507) to 99 (NS); and fell in Southeast England by 2.4 (NS) from 111 (41-180) to 108 (41-176). The falls in North Carolina and South Finland remained significant after allowances were made for changes in age, sex, and baseline mortality. Increased air conditioning probably explains the virtual disappearance of heat-related mortality in the hottest region, North Carolina, despite warmer summers. Other lifestyle changes associated with increasing prosperity probably explain the favorable trends in the cooler regions.

Aged↗
PubMed2003

Longitudinal changes in the nature, severity and frequency of COPD exacerbations.

Exacerbations are an important feature and outcome measure in chronic obstructive pulmonary disease (COPD), but little is known about changes in their severity, recovery, symptom composition or frequency over time. In this study 132 patients (91 male; median age 68.4 yrs and median forced expiratory volume in one second (FEV1) 38.4% predicted) recorded daily symptoms and morning peak expiratory flow. Patients were monitored for a median of 918 days and 1,111 exacerbations were identified. Patients with severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) category III, n=38) had an annual exacerbation frequency of 3.43 x yr(-1), 0.75 x yr(-1) higher than those with moderate COPD (GOLD II, n=94). Exacerbation frequency did not change significantly during the study. At exacerbation onset, symptom count increased to 2.23, relative to a baseline of 0.36 set 8-14 days previously, and this increase rose by 0.05 x yr(-1). Recovery to baseline levels in symptoms and FEV1 took longer (0.32 and 0.55 days x yr(-1)). Sputum purulence at exacerbation became more prevalent over time by 4.1% x yr(-1) from an initial value of 17%. The results of this study suggest that over time, individual patients have more symptoms during exacerbations, with an increased chance of sputum purulence and longer recovery times.

Aged↗
PubMed2002

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 (PaO(2)) 9.00 (8.3-9.5) kPa, forced expiratory volume in 1 second (FEV(1)) 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 FEV(1). 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 FEV(1) 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 FEV(1) 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 FEV(1) 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.

Administration, Inhalation↗
PubMed2002

Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are prone to frequent exacerbations which are a significant cause of morbidity and mortality. Stable COPD patients often have lower airway bacterial colonisation which may be an important stimulus to airway inflammation and thereby modulate exacerbation frequency. METHODS: Twenty nine patients with COPD (21 men, 16 current smokers) of mean (SD) age 65.9 (7.84) years, forced expiratory volume in 1 second (FEV(1)) 1.06 (0.41) l, FEV(1) % predicted 38.7 (15.2)%, FEV(1)/FVC 43.7 (14.1)%, inhaled steroid dosage 1.20 (0.66) mg/day completed daily diary cards for symptoms and peak flow over 18 months. Exacerbation frequency rates were determined from diary card data. Induced sputum was obtained from patients in the stable state, quantitative bacterial culture was performed, and cytokine levels were measured. RESULTS: Fifteen of the 29 patients (51.7%) were colonised by a possible pathogen: Haemophilus influenzae (53.3%), Streptococcus pneumoniae (33.3%), Haemophilus parainfluenzae (20%), Branhamella catarrhalis (20%), Pseudomonas aeruginosa (20%). The presence of lower airway bacterial colonisation in the stable state was related to exacerbation frequency (p=0.023). Patients colonised by H influenzae in the stable state reported more symptoms and increased sputum purulence at exacerbation than those not colonised. The median (IQR) symptom count at exacerbation in those colonised by H influenzae was 2.00 (2.00-2.65) compared with 2.00 (1.00-2.00) in those not colonised (p=0.03). The occurrence of increased sputum purulence at exacerbation per patient was 0.92 (0.56-1.00) in those colonised with H influenzae and 0.33 (0.00-0.60) in those not colonised (p=0.02). Sputum interleukin (IL)-8 levels correlated with the total bacterial count (rho=0.459, p=0.02). CONCLUSION: Lower airway bacterial colonisation in the stable state modulates the character and frequency of COPD exacerbations.

Aged↗
PubMed2001

Mortality related to cold and air pollution in London after allowance for effects of associated weather patterns.

We looked for atypical weather patterns that could confound, and explain large inconsistencies in, conventional estimates of mortality due to SO(2), CO, and smoke. Using Greater London data for 1976-1995 in the linear temperature/mortality range 0-15 degrees C we determined weather patterns associated with pollutants (all deseasonalized) by single regressions of daily temperature, wind, rain, humidity, and sunshine at successive days advance and delay. Polluted days were colder (P<0.01 for SO(2), CO, and smoke) and less windy and rainy than usual, and this cold weather was more prolonged than usual with 50% maximum temperature depression 5.9 days (95% interval 4.0-7.7) before high SO(2), compared to 2.0 (1.6-2.3) days before average cold days. We also used multiple regression of mortality at 50+ years of age on all these weather factors and pollutants at 0-, 1-, 2- to 4-, 5- to 13-, and 14- to 24-day delays to allow for the atypical weather patterns. This showed cold weather associated with 2.77 excess deaths per million during 24 days following a 1 degrees C fall for 1 day, but no net excess deaths with SO(2) (mean 28.0 ppb) or CO (1.26 ppm). It suggested (P>0.05) some increase with smoke, perhaps acting as surrogate for PM(10), for which data were too scanty to analyze.

Age Distribution↗
PubMed2001

Outdoor clothing: its relationship to geography, climate, behaviour and cold-related mortality in Europe.

It has been suggested, that the inhabitants of northern European regions, who experience little cold-related mortality, protect themselves outdoors by wearing more clothing, at the same temperature, than people living in southern regions where such mortality is high. Outdoor clothing data were collected in eight regions from 6583 people divided by sex and age group (50-59 and 65-74 years). Across Europe, the total clothing worn (as assessed by dry thermal insulation and numbers of items or layers) increased significantly with cold, wind, less physical activity and longer periods outdoors. Men wore 0.14 clo (1 clo = 0.115 m2 K W-1) more than women and the older people wore 0.05 clo more than the younger group (both P < 0.001). After allowance for these factors, regional differences in insulation and item number were correlated (r = -0.74, P = 0.037; r = -0.74, P = 0.036 respectively), but not those in clothing layers (r = -0.21; P = 0.61), with indices of cold-related mortality. Cold weather most increased the wearing of gloves, scarves and hats. The geographical variation in the wearing of these three together items more closely matched that in cold-related mortality (r = -0.89, P = 0.003). A possible explanation for this may be that they protect the head and hands, where stimulation by cold greatly increases peripheral vasoconstriction causing a rise in blood pressure that procedure haemoconcentration and raised cardiovascular risk.

Aged↗
PubMed2000

Heat related mortality in warm and cold regions of Europe: observational study.

OBJECTIVES: To assess heat related mortalities in relation to climate within Europe. DESIGN: Observational population study. SETTING: North Finland, south Finland, Baden-Württemberg, Netherlands, London, north Italy, and Athens. SUBJECTS: People aged 65-74. MAIN OUTCOME MEASURES: Mortalities at temperatures above, below, and within each region's temperature band of minimum mortality. RESULTS: Mortality was lowest at 14.3-17.3 degrees C in north Finland but at 22.7-25.7 degrees C in Athens. Overall the 3 degrees C minimum mortality temperature bands were significantly higher in regions with higher than lower mean summer temperatures (P=0.027). This was not due to regional differences in wind speeds, humidity, or rain. As a result, regions with hot summers did not have significantly higher annual heat related mortality per million population than cold regions at temperatures above these bands. Mean annual heat related mortalities were 304 (95% confidence interval 126 to 482) in North Finland, 445 (59 to 831) in Athens, and 40 (13 to 68) in London. Cold related mortalities were 2457 (1130 to 3786), 2533 (965 to 4101), and 3129 (2319 to 3939) respectively. CONCLUSIONS: Populations in Europe have adjusted successfully to mean summer temperatures ranging from 13.5 degrees C to 24.1 degrees C, and can be expected to adjust to global warming predicted for the next half century with little sustained increase in heat related mortality. Active measures to accelerate adjustment to hot weather could minimise temporary rises in heat related mortality, and measures to maintain protection against cold in winter could permit substantial reductions in overall mortality as temperatures rise.

Age Factors↗
PubMed2000

Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease.

Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. Patients recorded daily morning peak expiratory flow rate (PEFR) and changes in respiratory symptoms on diary cards. A subgroup of 34 patients also recorded daily spirometry. Exacerbations were defined by major symptoms (increased dyspnea, increased sputum purulence, increased sputum volume) and minor symptoms. Before onset of exacerbation there was deterioration in the symptoms of dyspnea, sore throat, cough, and symptoms of a common cold (all p < 0.05), but not lung function. Larger falls in PEFR were associated with symptoms of increased dyspnea (p = 0.014), colds (p = 0.047), or increased wheeze (p = 0.009) at exacerbation. Median recovery times were 6 (interquartile range [IQR] 1 to 14) d for PEFR and 7 (IQR 4 to 14) d for daily total symptom score. Recovery of PEFR to baseline values was complete in only 75.2% of exacerbations at 35 d, whereas in 7.1% of exacerbations at 91 d PEFR recovery had not occurred. In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.

Aged↗