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Biomedical subjects

A J Winning

Publications and source records attributed to A J Winning.

At least 19 recordsLinked to original sources

Reference values and prediction equations for normal lung function in a non-smoking white urban population.

Prediction equations for normal lung function have been derived from tests on 179 healthy, non-smoking, white urban dwellers. The subjects, 96 women (height 1.46-1.77 m) and 83 men (height 1.61-1.96 m) aged 18-86 years, underwent measurements of spirometric flow and volume, multi-breath helium dilution lung volumes, and single breath carbon monoxide transfer factor and the single breath nitrogen washout test. Regression analysis using height, age, and weight as independent variables was used to provide predicted values for both sexes. Correlation coefficients were similar to those found in previous studies but normal ranges for spirometic measurements were narrower than in many previous studies, and spirometric flow and volume measurements were higher than those obtained in studies that included cigarette smokers, reflecting our more stringent criteria for selecting subjects and the newer standardised technical methods adopted. Multi-breath helium dilution values for total lung capacity were similar to those found in previous studies but the inspiratory vital capacity was larger and the residual volume reduced. Values for carbon monoxide transfer factor and the single breath nitrogen washout did not differ significantly from existing values. A complete set of lung function reference values and prediction equations for both sexes has been derived from a single population. The exclusion of cigarette smokers and subjects with respiratory symptoms has produced values that should have a greater sensitivity in the detection of mild lung disease.

Adolescent↗

Effect on breathing of raising end-expiratory lung volume in sleeping laryngectomized man.

In animals, tonic vagal activity from lung receptors provides a means by which changes in end-expiratory lung volume can influence respiratory timing. We wished to examine whether increasing the end-expiratory lung volume within the tidal volume range had a similar effect in man. In order to minimize behavioral influences on breathing, the study was performed in subjects during deep non-rapid eye movement sleep. Five laryngectomized subjects were chosen for the study since their permanent tracheal stomata allow simple, airtight connection to respiratory apparatus and avoided problems with glottic closure. During EEG-documented sleep, end-expiratory volume was increased by up to 350 ml with the addition of expiratory threshold loads of 1 to 10 cm H2O. End-expiratory volume increased linearly with expiratory pressure. Inspiratory and expiratory times (TI and TE) were not affected by increases in end-expiratory volume. Tidal volume (VT) was decreased such that end-inspiratory volume remained unchanged. The decrease in VT may result from a reduction in inspiratory muscle efficiency at a higher lung volume. The results of the study provide no evidence that tonic vagal afferent information from the lungs is important in controlling respiratory rhythm within the tidal volume range in man when behavioral control of breathing is minimized.

Adult↗

Does the abnormal pattern of breathing in patients with interstitial lung disease persist in deep, non-rapid eye movement sleep?

Patients with interstitial lung disease (ILD) characteristically exhibit an increased ventilation and breathing frequency when awake. We wanted to see if these increases persisted during deep non-REM sleep. Using noninvasive techniques, we have quantified the pattern of breathing, arterial oxygen saturation, and transcutaneous PCO2 (PtcCO2) during standardized conditions of relaxed wakefulness and during Stage 4 (S4) sleep in eight patients with ILD and eight age-matched normal control subjects. The patients were given supplemental oxygen in order to prevent hypoxic ventilatory stimulation. The data were compared between the two groups during each of these states and also between states within each group. During wakefulness in the patients, respiratory frequency (f) and PtcCO2 were higher (p less than 0.001 and p less than 0.05, respectively) and inspiratory time (TI) and expiratory time (TE) were shorter (p less than 0.05 and p less than 0.001, respectively) than in the normal subjects. However, during S4 sleep, there were no significant differences between groups. Comparing wakefulness with S4 sleep: in the normal subjects during sleep, f and PtcCO2 were increased (p less than 0.01 and p less than 0.05, respectively), TE was shortened (p less than 0.01), and ventilation (VI) was unchanged. In contrast, in the patients, f decreased (p less than 0.001), TE lengthened (p less than 0.01), VI decreased (p less than 0.05), and the rise in PtcCO2 seen in the normal subjects during sleep did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The acute effect of cigarette smoking on the neutrophil elastase inhibitory capacity of peripheral lung lavage from asymptomatic volunteers.

Cigarette smoke-induced emphysema is thought to involve reduction of antielastolytic capacity, resulting in elevated elastase activity and lung tissue damage. Peripheral lavage collected from ten asymptomatic subjects immediately before and 20 min after smoking two high tar cigarettes was analysed for neutrophil elastase (NE) inhibitory capacity (IC), alpha 1-proteinase inhibitor (PI) function, elastolytic activity and immunoreactive levels of PI and bronchial inhibitor (BI). The only change found was a small fall in mol immunoreactive PI/mol albumin after smoking (approximately 17%, p less than 0.05) which did not affect NEIC, since PI contributed less than 50% of the NEIC. There was often more NEIC than mol BI + functional PI, suggesting the presence of other NE inhibitors. Thoracic computerized tomography scans of eight of these subjects highlighted two with emphysematous regions of lung; lavage from these two subjects contained either undetectable BI or inactive BI and this suggests a protective role for BI in emphysema.

Adult↗

The effect of lung inflation on breathing in man during wakefulness and sleep.

To determine whether the Hering-Breuer inflation reflex could be demonstrated in the presence and absence of behavioral influences on breathing, lung inflation was performed via the tracheal stoma in eleven laryngectomized subjects: seven seated at rest with their eyes closed and six recumbent during their deepest non-rapid eye movement sleep. Laryngectomized subjects were chosen for study since their permanent tracheal stoma and absence of a glottis abolished the sensation of inflation in the upper airways, avoided problems with glottic closure and allowed simple, airtight connection to respiratory apparatus. At rest awake, inflation volumes of 500-3050 ml caused no reproducible apnea. During EEG-documented sleep, the inflation reflex was tested on 75 occasions using inflation volumes of 540-2100 ml. On the 66 occasions not associated with subject arousal inflations exceeding approximately 1 L produced apnea terminated by inspiration; greater volumes gave longer apneas. At the end of the study the subjects were woken and retested; no reproducible apnea was found. We conclude that the Hering-Breuer inflation reflex can be demonstrated above the resting tidal volume range in adult man in the absence of the behavioral control of breathing.

Humans↗

Ventilation and breathlessness on maximal exercise in patients with interstitial lung disease after local anaesthetic aerosol inhalation.

1. The ventilatory response to maximal incremental exercise and the accompanying sensation of breathlessness were studied after the inhalation of 0.9% sodium chloride (saline) and 5% bupivacaine aerosols in six patients with interstitial lung disease. 2. The adequacy of airway anaesthesia induced by bupivacaine aerosol was confirmed by the absence of the cough reflex to 5% citric acid aerosol on completion of exercise. 3. All subjects first performed a trial exercise test to familiarize them with the procedure and to assess the degree of arterial oxygen desaturation on exercise. In subsequent tests, supplementary oxygen was given to maintain the saturation at 95% or above. 4. Airway anaesthesia had no effect on the ability to perform exercise as assessed by maximum workload, CO2 production or heart rate. No significant changes were seen on the pattern of breathing, minute ventilation or end-tidal PCO2 on exercise. There was, however, a small but statistically significant increase in ventilation related to CO2 production (VE/VCO2) at the end of exercise. 5. There was a tendency for breathlessness to be increased by airway anaesthesia but this did not reach statistical significance. 6. These results provide no evidence that vagal afferent activity is responsible for the abnormal ventilatory response to exercise in patients with interstitial lung disease. The perception of breathlessness in these patients was not diminished by anaesthesia of the airway.

Aerosols↗

Comparison of human lung surface protein profiles from the central and peripheral airways sampled using two regional lavage techniques.

This study describes two new techniques of lung lavage which selectively remove material from the central airways, or from the lung below the seventh generation. Bronchograms confirmed that discrete regions of the lung were washed by central lavage (CL; maximum airway diameter approximately 6.5 mm) and peripheral lavage (PL; maximum airway diameter approximately 1.3 mm), and that both could be clearly distinguished from conventional bronchoalveolar lavage (BAL). These techniques were used to establish whether or not large-airway proteins made a major contribution to the protein profile of BAL. Twenty consecutive patients undergoing routine fibreoptic bronchoscopy were investigated. More bronchial mucus proteinase inhibitor per unit albumin and per unit total measured antiproteinase was present in CL than PL or BAL. In contrast alpha 1-proteinase inhibitor per unit albumin and as a percentage of total measured antiproteinase was lower in CL than in other lavage types. There were no differences in elastase activity, irrespective of the way in which the data were expressed. As no differences were found between BAL and PL for any of the variables measured, it was concluded that in the subjects studied the contribution of CL proteins to BAL was minimal.

Adult↗

Blockade of 'alveolar' and airway reflexes by local anesthetic aerosol in dogs.

To determine whether local anesthetic aerosol could selectively block a reflex thought to originate from the alveoli, two small particle bupivacaine aerosols (mass median diameters 1.0 and 1.7 micron) were administered on separate occasions to spontaneously breathing anesthetized dogs. Both aerosols resulted in a small but statistically significant increase in VT and one produced an increase in f. The pulmonary chemoreflex to right heart injection of capsaicin, the cough reflex and the Hering-Breuer inflation reflex were unaffected. The ability of a large particle aerosol (mass median diameter 4.8 micron) to block these reflexes was also assessed. This aerosol produced a progressive slowing and deepening of breathing which was maximal after 20 min of aerosol inhalation. Ten min of this aerosol attenuated the pulmonary chemoreflex and abolished the cough and inflation reflexes; 20 min abolished all reflexes. These had recovered by about 1 h after aerosol. Intravenous bupivacaine had no effect on breathing or any reflex. We conclude that a local anesthetic aerosol can block reflexes arising from the alveoli, but not selectively.

Aerosols↗

Aerosol anesthesia increases hypercapnic ventilation and breathlessness in laryngectomized humans.

The effect of local anesthetic aerosol inhalation on the ventilatory response and the sensation of breathlessness to CO2 rebreathing was studied in seven healthy male subjects with permanent tracheal stomas after laryngectomy for carcinoma. Inhalation of bupivacaine aerosol sufficient to abolish the cough reflex to mechanical probing below the carina increased the ventilatory response to CO2 in six of seven subjects compared with saline control. This was achieved by an increase in both respiratory frequency (f) and tidal volume (VT) in four subjects, f in one subject, and VT in one subject. All subjects reported that they were more breathless on rebreathing after bupivacaine aerosol. The six subjects who recorded breathlessness with a visual analog scale (VAS) indicated its onset at a lower minute ventilation (VE) and gave higher VAS scores for equivalent levels of VE after threshold. We conclude that the enhanced CO2 sensitivity and breathlessness on rebreathing after airway anesthesia results from altered lower airway receptor discharge.

Aged↗

Effects of cigarette smoking and drugs on respiratory tract proteases and antiproteases.

Increased pulmonary proteolytic (elastolytic) activity is thought to be the primary cause of emphysema and may also play a rôle in the pathology of bronchitis. These diseases are common amongst tobacco smokers. Serum-derived alpha 1-proteinase inhibitor (alpha 1PI) and locally produced protease inhibitors normally protect the pulmonary epithelium from proteolytic attack, but tobacco smoke can inactivate these antiproteases by oxidative and non-oxidative mechanisms. Bronchoalveolar lavage fluid (BALF) samples lung surface components and most studies show that there is elevated elastolytic activity in smokers' BALF. Whether antiproteolytic capacity is reduced in these samples remains debatable. A selective lavage technique is described which independently samples central and peripheral epithelium from the same subject. Analysis demonstrates a protease-antiprotease imbalance which can differ in central and peripheral lavage and which could be significant in the development of obstructive airways disease. Therapeutic approaches include augmenting antiprotease potential using genetically engineered, oxidant-resistant alpha 1PI or synthetic peptide inhibitors.

Epithelium↗

Respiratory and cardiovascular effects of central and peripheral intravenous injections of capsaicin in man: evidence for pulmonary chemosensitivity.

The respiratory and cardiovascular effects of capsaicin injection into the superior vena cava and an arm vein were studied in three normal subjects. No changes were seen in tidal volume, inspiratory time or expiratory time after capsaicin injection. Instantaneous heart rate, systolic blood pressure and diastolic blood pressure remained unchanged. Central and peripheral intravenous injections of capsaicin but not control solution above a threshold of 0.5 micrograms/kg produced dose-dependent sensations sequentially in the chest, face, rectum and extremities. The chest sensation, a 'raw, burning' feeling, occurred 3-4 s after central capsaicin injection. No subject reported feeling breathless. In one subject the maximum tolerable dose of capsaicin (4 micrograms/kg) produced paroxysmal coughing 3.9 s after a central injection. In two of the subjects capsaicin injection was repeated after inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter 4.8 micron), sufficient to block the cough reflex to a 5% citric acid aerosol. Prior inhalation of local anaesthetic aerosol abolished the chest sensation after capsaicin injection; the other sensations were unaffected. This study demonstrates that stimulation of receptors accessible from the pulmonary vascular bed does not evoke the pulmonary chemoreflex in conscious man but can produce coughing. It provides evidence for the existence of a nociceptive system of nerve endings in the lung parenchyma that can be blocked by inhaled local anaesthetic aerosol.

Bupivacaine↗

Interpretation of negative results in fine needle aspiration of discrete pulmonary lesions.

A retrospective analysis was carried out on a consecutive series of 181 percutaneous fine needle aspiration biopsies of discrete pulmonary lesions, in which the outcome was established in 95%. In primary bronchial carcinoma the technique had a sensitivity of 86%. There was no relationship between the size, location, or radiological appearance of the lesion and the incidence of false negative results. The principal reason for failure to diagnose malignancy was inadequacy of the material provided for cytological examination. For metastatic neoplasms of non-bronchial origin the procedure had a sensitivity of 42% and a significantly greater false negative rate than for primary bronchial malignancy. For the entire series 72 (40%) of the procedures failed to produce a definite diagnosis, 29 (40%) of these cases subsequently proving to be malignant. A positive diagnosis was established in only 16% of patients with benign conditions. Review of published reports and consideration of the role of this and other biopsy techniques in the investigation of discrete pulmonary lesions lead to the conclusion that needle aspiration biopsy seems particularly appropriate in the investigation of inoperable patients with probable bronchial carcinoma in whom sputum cytology and bronchoscopy do not yield a diagnosis.

Biopsy, Needle↗

The effect of airway anaesthesia on the control of breathing and the sensation of breathlessness in man.

The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 micron), was studied in 12 normal subjects. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc. Bupivacaine labelled in this way was deposited primarily in the central airways. The effectiveness and duration of airway anaesthesia were assessed by the absence of the cough reflex to the inhalation of three breaths of a 5% citric acid aerosol. Airway anaesthesia always lasted more than 20 min. Resting ventilation was measured, by respiratory inductance plethysmography, before and after inhalation of saline and bupivacaine aerosols. The ventilatory response to maximal incremental exercise and, separately, to CO2 inhalation was studied after the inhalation of saline and bupivacaine aerosols. Breathlessness was quantified by using a visual analogue scale (VAS) during a study and by questioning on its completion. At rest, airway anaesthesia had no effect on mean tidal volume (VT), inspiratory time (Ti), expiratory time (Te) or end-tidal PCO2, although the variability of tidal volume was increased. On exercise, slower deeper breathing was produced and breathlessness was reduced. The ventilatory response to CO2 was increased. The results suggest that stretch receptors in the airways modulate the pattern of breathing in normal man when ventilation is stimulated by exercise; their activation may also be involved in the genesis of the associated breathlessness. A hypothesis in terms of a differential airway/alveolar receptor block, is proposed to explain the exaggerated ventilatory response to CO2.

Adult↗