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Biomedical subjects

N B Pride

Publications and source records attributed to N B Pride.

At least 37 records · Page 2Linked to original sources

In defence of the carbon monoxide transfer coefficient Kco (TL/VA).

The carbon monoxide transfer factor (TL,co) is the product of the two primary measurements during breath-holding, the CO transfer coefficient (Kco) and the alveolar volume (VA). Kco is essentially the rate constant for alveolar CO uptake (Krogh's kco), and in healthy subjects, increases when VA is reduced by submaximal inflation, or when pulmonary blood flow increases. Recently, new reference values were proposed for clinical use which included the observed VA at full inflation; this was claimed to "eliminate the need for Kco". In this commentary, some mechanisms e.g. respiratory muscle weakness, lung resection, diffuse alveolar damage and airflow obstruction, which decrease or increase total lung capacity (TLC) are reviewed. Even when alveolar structure and function are normal, the change in Kco at a given VA varies according to the underlying pathophysiological mechanism. The advantages and disadvantages of normalizing Kco and TL,co to predisease predicted TLC or to the patient's actual VA (using lack of expansion or loss of alveolar units models) are considered. Examination of carbon monoxide transfer coefficient and alveolar volume separately provides information on disease pathophysiology which cannot be obtained from their product, the carbon monoxide transfer factor.

Airway Resistance↗

Estimation of diaphragm length in patients with severe chronic obstructive pulmonary disease.

In patients with advanced chronic obstructive pulmonary disease (COPD) diaphragm function may be compromised because of reduced muscle fibre length. Diaphragm length (L(Di)) can be estimated from measurements of transverse diameter of the rib cage (D(Rc)) and the length of the zone of apposition (L(Zapp)) in healthy subjects, but this method has not been validated in patients with COPD. Postero-anterior chest radiographs were obtained at total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) in nine male patients with severe COPD (mean [S.D.]; FEV(1), 23 [6] %pred.; FRC, 199 [15] %pred.). Radiographs taken at TLC were used to identify the lateral costal insertions of the diaphragm (L(Zapp) assumed to approach zero at TLC). L(Di) was measured directly and also estimated from measurements of L(Zapp) and D(Rc) using a prediction equation derived from healthy subjects. The estimation of L(Di) was highly accurate with an intraclass correlation coefficient of 0.93 and 95% CI of approximately +/-8% of the true value. L(Di) decreased from 426 (64) mm at RV to 305 (31) mm at TLC. As there were only small and variable changes in D(Rc) across the lung volume range, most of the L(Di) changes occurred in the zone of apposition. Additional studies showed that measurements of L(Di) from PA and lateral radiographs performed at different lung volumes were tightly correlated. These results suggest that non-invasive measurements of L(Zapp) in the coronal plane (e.g. using ultrasonography) and D(Rc) (e.g. using magnetometers) can be used to provide an accurate estimate of L(Di) in COPD patients.

Aged↗

Tumour necrosis factor-alpha gene promoter polymorphism in chronic obstructive pulmonary disease.

Tumour necrosis factor(TNF)-alpha levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-alpha gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians. Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood. There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung). It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease.

Aged↗

Changes in carbon monoxide transfer over 22 years in middle-aged men.

We measured single breath CO transfer (T(LCO)), single breath alveolar volume (VA), CO transfer coefficient (K(CO)) and forced expiratory volume in 1 sec (FEV1) in 84 men, mean age 40.5 years at recruitment, in 1975 and in 1997. At recruitment, 42 men were cigarette smokers and 42 were not smoking. Mean annual decline in FEV1 was similar in never- (34.2 ml yr(-1)) and ex- (33.1 ml yr(-1)) smokers and faster (51.0 ml yr(-1)) in continuing smokers. In contrast to predictions from cross-sectional reference values, there was no fall in T(LCO) or K(CO) in men who did not smoke over the period of follow-up. In the 16 men who smoked throughout follow-up there was a 10% fall in T(LCO) (P = 0.043) but most of this was due to a significant fall in VA (P = 0.017), presumably reflecting uneven gas mixing. These results indicate the need for population-based longitudinal studies of T(LCO) and K(CO). If single breath estimates of VA are used in subjects with even mild airflow obstruction, K(CO) rather than T(LCO) should be used to assess alveolar function.

Adult↗

Recent trends in physician diagnosed COPD in women and men in the UK.

BACKGROUND: Recent trends in physician diagnosed chronic obstructive pulmonary disease (COPD) in the UK were estimated, with a particular focus on women. METHODS: A retrospective cohort of British patients with COPD was constructed from the General Practice Research Database (GPRD), a large automated database of UK general practice data. Prevalence and all-cause mortality rates by sex, calendar year, and severity of COPD, based on treatment only, were estimated from January 1990 to December 1997. RESULTS: A total of 50 714 incident COPD patients were studied, 23 277 (45.9%) of whom were women. From 1990 to 1997 the annual prevalence rates of physician diagnosed COPD in women rose continuously from 0.80% (95% CI 0.75 to 0.83) to 1.36% (95% CI 1.34 to 1.39), (p for trend <0.01), rising to the rate observed in men in 1990. Increases in the prevalence of COPD were observed in women of all ages; in contrast, a plateau was observed in the prevalence of COPD in men from the mid 1990s. All-cause mortality rates were higher in men than in women (106.8 versus 82.2 per 1000 person-years), with a consistently increased relative risk in men of 1.3 even after controlling for the severity of COPD. Significantly increased mortality rates were also observed in adults aged less than 65 years. The mean age at death was 76.5 years; patients with severe COPD died an average of three years before those with mild disease (p<0.01) and four years before the age and sex matched reference population. CONCLUSIONS: While prevalence rates of COPD in the UK seem to have peaked in men, they are continuing to rise in women. This trend, together with the ageing of the population and the long term cumulative effect of pack-years of smoking in women, is likely to increase the present burden of COPD in the UK.

Aged↗

Effect of supine posture on respiratory mechanics in chronic left ventricular failure.

The mechanisms of orthopnea and the role of changes in respiratory mechanics in left ventricular failure (LVF) are poorly understood. We have measured total respiratory airflow resistance (Rrs) using forced oscillation in the sitting and supine positions in 10 patients with chronic LVF (NYHA II-III) shortly after recovery from acute LVF and in 10 matched control subjects (CON). Seated, the patients with LVF had small lung volumes but no evidence of airway obstruction (mean FEV(1)/FVC, 81%). Mean Rrs at 6 Hz was only slightly higher in LVF (3.4 cm H(2)O. L(-1). s) than in CON (2.6 cm H(2)O. L(-1). s). After 5 min supine, breathlessness in LVF increased. Despite much smaller mean falls in mid-tidal lung volume (MTLV) in LVF than in CON, the supine rise in Rrs was 80.5% in LVF and 37.6% in CON; mean increases in specific Rrs (SRrs = Rrs.MTLV) were 75.8% in LVF and 16.6% in CON (p 0.001). Five minutes after resuming the sitting position all values had reverted almost to the original sitting values. In 5 LVF patients, nebulized ipratropium, a muscarinic antagonist, only slightly attenuated the supine rise in SRrs. We conclude that patients with chronic LVF, who had little evidence of airways obstruction when seated, showed a large rise in airflow resistance after lying supine for 5 min. This cannot be attributed to reduction in lung volume when supine and no evidence was found of vagally-induced bronchoconstriction. Further experiments are required to establish the cause of the rapid supine rise in airflow resistance in LVF.

Aged↗

Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. RESULTS: Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups. CONCLUSIONS: In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.

Administration, Inhalation↗

The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies.

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.

Administration, Inhalation↗

Use of mouth pressure twitches induced by cervical magnetic stimulation to assess voluntary activation of the diaphragm.

There is a need for a simple method to assess the adequacy of diaphragm activation during voluntary inspiratory efforts in patients with suspected respiratory muscle weakness. We have compared mouth (Pmo,t), oesophageal (Poes,t) and transdiaphragmatic (Pdi,t) twitch pressure elicited by cervical magnetic stimulation (CMS) in five normal men (mean (SD) age 32.2 (1.8) yrs) on two separate study days. Single magnetic stimuli were delivered at functional residual capacity during relaxation and during graded voluntary inspiratory efforts against a closed airway. As voluntary-effort transdiaphragmatic and oesophageal pressure increased, Pdi,t and Poes,t decreased linearly (r range, respectively, 0.82-0.98 and 0.87-0.95). During relaxation, Pmo,t was unreliable due to the poor transmission of intrathoracic pressure, but during inspiratory efforts, the relation between voluntary mouth pressure and Pmo,t was also linear (r range 0.84-0.95). On average, our subjects voluntarily generated 99, 100 and 102% of the maximum transdiaphragmatic, oesophageal and mouth pressures predicted by the respective linear regression equations. Pmo,t was correlated to both Poes,t and Pdi,t during inspiratory efforts, but not during relaxation. These studies confirm that twitch pressures induced by CMS during inspiratory efforts can be assessed at the mouth in normal subjects, providing a simple and non-invasive technique for assessing diaphragm activation during voluntary inspiratory efforts. Potentially, this technique could be made more sensitive and accurate and applied to detect submaximal efforts in patients.

Adult↗

Use of nasal peak flow to assess nasal patency.

Nasal patency is usually assessed in the laboratory by measuring nasal airflow conductance (Gnaw); peak inspiratory and/or expiratory flow measurements via the nose (PIFna, PEFna) have been proposed as simple alternatives suitable for home monitoring of rhinitis. We have compared the scale of changes in PIFna and PEFna (measured with a pneumotachograph) with changes in Gnaw (measured by the forced-oscillation technique) when nasal patency was increased by a topical alpha-adrenergic agonist, xylometazoline (five control subjects, seven with seasonal rhinitis, studied when asymptomatic) or decreased by topical histamine (eight control subjects). In further experiments, we altered intrapulmonary airway calibre by having subjects inhale histamine or salbutamol aerosols and examined effects on the configuration of nasal flow-volume curves (six subjects with rhinitis and mild asthma). After topical xylometazoline, there was a mean 283% increase in Gnaw, 80% increase in PEFna, and 63% increase in PIFna. After topical histamine, there was a mean 72% decrease in Gnaw, 38% decrease in PEFna, and 39% decrease in PIFna. Inducing intrapulmonary airway obstruction sometimes obscured changes in nasal patency by removing the effects of added nasal resistance on expiration and preventing development of flow limitation in the nose on inspiration. Thus, after topical drug treatment to the nose, changes in Gnaw were considerably larger than in PEFna or PIFna, which were proportionately similar. Because PIFna is usually restricted by nasal flow limitation, it is probably superior to PEFna for assessing nasal patency. When effort is submaximal, intrapulmonary dynamic resistance is increased, or nasal dynamic resistance is low, PEFna and PIFna can give a misleading impression of nasal patency. These errors can be avoided by comparisons with mouth PEF and/or PIF, suggesting that nasal and mouth peak flow should both be measured during home monitoring.

Adult↗

Diaphragm thickness and inspiratory strength in patients with Duchenne muscular dystrophy.

BACKGROUND: There is little information on the morphometric characteristics of the diaphragm in patients with Duchenne muscular dystrophy. METHODS: The thickness of the diaphragm was measured at the zone of apposition using B mode ultrasonography in 10 boys with Duchenne muscular dystrophy of mean (SD) age 10.3 (1.3) years and 12 normal controls of mean (SD) age 11.3 (2.0) years during relaxation (DiTrelax) and during maximum effort inspiratory manoeuvres (DiTPimax) at functional residual capacity. RESULTS: DiTrelax was greater in the patients with Duchenne muscular dystrophy (1.74 (0.21) mm) than in controls (1.48 (0.20) mm), mean difference (95% CI) 0.26 (0.08 to 0.44), despite considerable impairment of maximum effort inspiratory mouth pressure (Pimax) (patients with Duchenne muscular dystrophy -37 (8) cm H2O, controls -80 (33) cm H2O), mean difference (95% CI) 43 (65 to 20). During a Pimax manoeuvre, compared with measurements taken during relaxation, the diaphragm thickened 1.6 times in patients with Duchenne muscular dystrophy and 2.3 times in controls (DiTPimax 2.62 (0.7) mm and 3.5 (0.85) mm, respectively), mean difference (95% CI) -0.88 (-1.58 to -0.18). CONCLUSIONS: Resting diaphragm thickness is increased in young patients with Duchenne muscular dystrophy with impaired respiratory muscle force. This finding could be analogous to the pseudo-hypertrophy that is observed in some limb muscle groups.

Child↗

Size and strength of the respiratory and quadriceps muscles in patients with chronic asthma.

There have been few studies of respiratory and limb muscle size and function in middle-aged patients with asthma and persistent airways obstruction. We have compared the forces generated by the respiratory and thigh muscles with their dimensions assessed by ultrasound in nine middle-aged patients with chronic asthma (mean age 56 (SD 8) yrs; functional residual capacity/total lung capacity ratio (FRC/TLC) 60 (10)%), and in nine normal subjects (aged 53 (7) yrs; FRC/TLC 55 (5)%). Diaphragm thickness was measured at the zone of apposition by B-mode ultrasound during relaxation (DiTrelax) and during a maximum-effort inspiratory manoeuvre (DiTpI,max) at FRC. Cross-sectional area of the relaxed rectus femoris muscle (ARF) was determined by ultrasound at mid-thigh level. Isometric strength of the right quadriceps muscle group was measured during maximum voluntary contraction. Asthmatic patients had preserved quadriceps strength and ARF but moderately impaired maximum inspiratory pressure (PI,max) (-52 (18) cmH2O) and thicker DiTrelax (2.2 (0.4) mm), compared to normal subjects (-73 (21) cmH2O and 1.7 (0.3) mm, respectively). Middle-aged patients with chronic asthma and a small increase in functional residual capacity/total lung capacity ratio have preserved limb muscle force and dimensions, modestly impaired inspiratory muscle strength, and slightly increased thickness of the costal diaphragm. Future studies of respiratory muscle function in asthma should be aided by measurement of diaphragm thickness and of limb muscle strength and size. Such studies are required particularly in older patients with severe hyperinflation who are most likely to have impairment of muscle function.

Airway Obstruction↗

Dissociation of neutrophil emigration and metabolic activity in lobar pneumonia and bronchiectasis.

In animal models of pulmonary inflammation, neutrophils exhibit a dramatic influx of glucose in periods of high metabolic activity. This information was utilized to develop a technique, involving positron emission tomography (PET) of 2-[18F]-fluoro-2-deoxy-D-glucose (18FDG), which measures neutrophil activity in situ. This technique was applied in a comparative study of neutrophil function in patients with acute lobar pneumonia or bronchiectasis. Neutrophil emigration was measured by gamma-scintigraphy of intravenously injected 111In-labelled granulocytes and neutrophil activity determined by PET of 18FDG. Neutrophil emigration was evident in 4 out of 5 bronchiectasis patients, whilst no emigration was apparent in the two pneumonia patients studied, consistent with animal studies showing maximum emigration soon after challenge. In contrast, 18FDG uptake was markedly increased in 4 out of 5 pneumonia patients but not in the patients with bronchiectasis. Localization of radioactivity to neutrophils was confirmed by microautoradiography of lavage fluid in a patient with pneumonia. These results suggest that the elevated uptake of glucose by neutrophils during the inflammatory response is a postmigratory event, most likely reflecting the respiratory burst, and that high levels of neutrophil emigration are not necessarily associated with significantly increased metabolic activity of these cells.

Adult↗

Imaging allergen-invoked airway inflammation in atopic asthma with [18F]-fluorodeoxyglucose and positron emission tomography.

BACKGROUND: Airway inflammation is a feature of asthma and can be quantified invasively with bronchial lavage and endobronchial histology. Inflammatory foci can be imaged non-invasively with positron emission tomography (PET) and [18F]-fluorodeoxyglucose (18FDG) to quantify glucose uptake in activated granulocytes. We used this technique to study airway inflammation in asthma. METHODS: Nine men with mild atopic asthma were studied. In five, we studied the effect of bronchoscopic segmental allergen challenge on 18FDG uptake. Allergen was instilled into the posterior segment of the right upper lobe; a similar volume (20 mL) of isotonic saline was instilled into the posterior segment of the left upper lobe. At 1-32 h after instillation, PET with 18FDG was done. In the other four patients, we administered aerosolised allergen. FINDINGS: 18FDG uptake was increased four-fold in the right compared with the left upper lobe (geometric mean of ratios 4.30, 95% Cl 2.39-7.72, p=0.002). Aerosolised administration of allergen did not significantly increase 18FDG uptake. INTERPRETATION: These data show that local allergen-invoked airway inflammation can be visualised with 18FDG and PET in asthma. The cellular localisation of the 18FDG signal remains to be determined.

Adult↗

Capsaicin cough sensitivity increases during upper respiratory infection.

The mechanism of cough associated with upper respiratory infection (URI) is poorly understood. This paper reports a study of the role of altered sensitivity of capsaicin-sensitive airway nerves. In a prospective study, baseline (B) capsaicin-induced cough and methacholine-induced airway responsiveness were measured in 103 healthy volunteers. During the following year, 31 subjects reattended for challenge testing during URI (I) and after recovery (R). The log concentration of capsaicin required to elicit two coughs (C2) was significantly lower during infection than recovery but not baseline [median (interquartile range) B = 0.59 (0.28-1.20), I = 0.27 (0-0.89), R = 0.89 (0.28-1.49)]. Log C5 (concentration causing five coughs) was lower during infection than baseline and recovery [B = 1.79 (1.20-2.70), I = 1.49 (0.89-2.08), R = 1.79 (1.20-2.40)]. FEV1 and PC15 methacholine values were unchanged during infection compared to baseline. Subjects with dry cough (n = 14) had lower C5 values during infection than both baseline and recovery, and lower C2 values during infection than recovery; in these subjects, increase in capsaicin sensitivity correlated with cough severity score. Subjects with productive cough or no cough showed no consistent changes during infection. Twenty-six control subjects who reattended without URI showed no change in capsaicin sensitivity. Upper respiratory infection may cause cough as a result of increased sensitivity of capsaicin-sensitive afferent airway nerves without affecting airway calibre or responsiveness.

Administration, Inhalation↗

Topical corticosteroids potentiate mucin secretion in the normal nose.

The exact mode of action of topical nasal corticosteroids is still uncertain. The aim of this study was to determine their effects on microvascular permeability and cellular and glandular secretion by measuring the levels of total protein, albumin, lysozyme and mucin recovered in nasal lavage fluid before and after 3 weeks of treatment with a topical nasal corticosteroid in 12 normal non-atopic subjects. Six subjects applied 200 micrograms fluticasone propionate and six applied 200 micrograms beclomethasone dipropionate to one nostril in each 24 h: matched placebo was applied to the other nostril. There was a significant rise in the level of mucin recovered compared with baseline values following fluticasone administration (baseline 76.2 micrograms/ml (mean) +/- 5.5 (SEM), fluticasone 118.3 micrograms/ml +/- 11.6 P = 0.015) and beclomethasone administration (baseline 64.3 micrograms/ml +/- 6.6, beclomethasone 87.2 micrograms/ml +/- 4.8, P = 0.041). There was no significant change in the levels of total protein, albumin or lysozyme following either active medication or placebo treatment. Topical corticosteroids appear to potentiate mucin secretion and do not alter serous secretion or microvascular permeability in the unchallenged non-atopic nose.

Administration, Topical↗