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1.
Respiration ; 61(2): 68-73, 1994.
Article in English | MEDLINE | ID: mdl-8008990

ABSTRACT

Our objective was to examine the changes in regional ventilation during histamine-induced bronchoconstriction in stable asthma. We measured regional ventilation by a new method which measures regional distribution of inhaled 127Xe during tidal breathing by a gated method and, by simultaneously measuring 99mTc counts from labelled macroaggregates, allowed for changes in lung shape during the breathing cycle. We studied 10 asthmatic patients [forced expiratory volume in 1 s (FEV1 2.04-4.37 litres)] and measured, in addition to the regional ventilation, oxygen saturation (SaO2), minute ventilation (VE) and tidal volume (Vt) before and after inhaling enough histamine to lower FEV1 by > 20% and/or SaO2 by > 4%. Histamine inhalation reduced FEV1 by 0.44-1.15 liters and SaO2 by 0-4%. It increased VE and functional residual capacity (FRC) in 8 of the 10 patients. The FEV1 fall did not correlate with the SaO2 fall, VE or FRC changes. Histamine inhalation increased apical ventilation in most patients, but the changes in regional ventilation in the left and right lungs were asymmetrical in 17 out of the 30 lung regions studied (upper, middle and lower paired regions in 10 patients). These results demonstrate that histamine bronchial challenge causes uneven regional ventilation. Any resultant change in ventilation-perfusion balance may be the underlying mechanism of oxygen desaturation seen in this procedure and in spontaneous attacks of asthma.


Subject(s)
Asthma/physiopathology , Bronchial Provocation Tests , Histamine , Respiration , Adult , Asthma/blood , Asthma/diagnostic imaging , Bronchoconstriction/physiology , Female , Forced Expiratory Volume/drug effects , Functional Residual Capacity/drug effects , Humans , Lung/diagnostic imaging , Male , Middle Aged , Oxygen/blood , Radionuclide Imaging
2.
J Theor Biol ; 166(2): 135-47, 1994 Jan 21.
Article in English | MEDLINE | ID: mdl-8145565

ABSTRACT

We have developed a mathematical model to describe the dynamic ventilatory response to hypoxia. The ventilatory response to both transient (two to three breaths nitrogen) and 3 min step change hypoxic stimuli were measured in ten normal subjects during moderate exercise (oxygen consumption 0.96 +/- 0.08 1 min-1). The simplest model relating ventilation to ear oxygen saturation which adequately described the responses in all subjects consisted of two linear differential equations in parallel; both using the fall in oxygen saturation as input, and with the outputs summed to give the rise in ventilation. One equation had a fast time constant (< 3 sec), and the other a slow time constant. Non-linear terms included were (i) a "saturating" effect, similar to that described by the Michaelis-Menten equation, reducing the gain of the equation with the slow time constant as oxygen saturation falls, and (ii) "inhibition" or "potentiation" of the gain of the equation with a slow time constant as the output of the fast time constant equation increased. Repeated measurements in four subjects showed intra- and inter-subject variability for all parameters, with significant between-subject variability for the gain of the fast time constant equation. The final model structure is similar to that describing the peripheral chemoreceptor-mediated hypoxic ventilatory response in anaesthetized cats.


Subject(s)
Computer Simulation , Hypoxia/physiopathology , Lung/physiopathology , Adult , Female , Humans , Male , Models, Biological
3.
Thorax ; 47(7): 494-8, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1412090

ABSTRACT

BACKGROUND: The relation between pulmonary disease and physiological abnormality in patients with hypoxic cor pulmonale is controversial and the association between arterial hypoxaemia and right ventricular hypertrophy has been challenged. To address these problems matched patients treated with and without domiciliary oxygen were studied. METHODS: Necropsy data were obtained on 19 patients (14 male), 10 of whom had been treated with domiciliary oxygen. Pulmonary artery pressure and total pulmonary vascular resistance as well as blood gas tensions during the breathing of air and oxygen were available for the six months before death. Formalin fixed lung slices were assessed for panacinar and centriacinar emphysema. Right and left ventricular weights were measured and their ratio (LV&S/RV) was used as an index of right ventricular hypertrophy. Carotid body weights were available in 14 cases. RESULTS: Fourteen patients died of respiratory failure and antemortem thrombus was found in the pulmonary arteries of eight cases. Physiological measurements were unrelated to the degree of macroscopic emphysema, pulmonary hypertension, or daytime blood gas tensions. When allowance was made for the higher "ambient" arterial oxygen tension (PaO2) of those who had oxygen, PaO2 was correlated with LV&S/RV (r = 0.79), absolute right ventricular weight (r = -0.53), and carotid body weight (r = 0.68). CONCLUSIONS: These data show that in hypoxic cor pulmonale in vivo physiological disturbances are poor indicators of the underlying disease process. The relation of "ambient" PaO2 to right ventricular hypertrophy and carotid body weight suggests that domiciliary oxygen therapy might lead to regression of such established disease.


Subject(s)
Pulmonary Heart Disease/pathology , Pulmonary Heart Disease/physiopathology , Blood Pressure/physiology , Cardiomegaly/pathology , Carotid Body/pathology , Female , Heart Ventricles/pathology , Humans , Hypoxia/physiopathology , Male , Middle Aged , Organ Size , Oxygen/blood , Oxygen Inhalation Therapy , Pulmonary Artery/physiopathology , Pulmonary Emphysema/pathology , Pulmonary Heart Disease/therapy , Vascular Resistance/physiology
4.
Thorax ; 47(1): 34-40, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1539142

ABSTRACT

BACKGROUND: On the basis of a retrospective survey by this unit it was suggested that patients with acute ventilatory failure should be given sufficient controlled oxygen treatment to raise the arterial oxygen tension (PaO2) to above 6.6 kPa, with the addition of a respiratory stimulant if the hydrogen ion concentration ([H+]) rose above 55 nmol/l and assisted ventilation if the patient remained acidotic despite these measures. This study was designed to verify the prognostic factors that determine survival in acute ventilatory failure and determine the outcome when our guidelines were implemented. METHODS: One hundred and thirty nine episodes of acute hypercapnic (type II) respiratory failure were studied prospectively in 95 patients admitted with acute exacerbations of chronic obstructive lung disease. Patients had to have a PaO2 below 6.6 kPa and an arterial carbon dioxide tension (PaCO2) above 6.6 kPa while breathing air. RESULTS: The mortality associated with episodes of acute ventilatory failure was 12%. Patients who died tended to be older and were significantly more acidotic, hypotensive, and uraemic on admission than those who survived, but they had similar degrees of hypoxaemia and hypercapnia. Death occurred in 10 of the 39 episodes in which arterial [H+] rose to 55 nmol/l or above, compared with seven of the 100 episodes in which it remained below 55 nmol/l. The respiratory stimulant doxapram was used in 37 episodes and was associated with a reduction in [H+] below 55 nmol/l within 24 hours in 23 episodes. Assisted ventilation was used in only four episodes. CONCLUSION: Arterial [H+] is an important prognostic factor for survival. Most patients treated according to the guidelines outlined above can be managed successfully without assisted ventilation.


Subject(s)
Hypercapnia/complications , Lung Diseases, Obstructive/complications , Respiratory Insufficiency/complications , Doxapram/therapeutic use , Female , Humans , Hydrogen-Ion Concentration , Hypercapnia/blood , Hypercapnia/drug therapy , Lung Diseases, Obstructive/blood , Lung Diseases, Obstructive/drug therapy , Male , Oxygen/blood , Prognosis , Respiratory Insufficiency/blood , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/mortality , Retrospective Studies , Risk Factors
5.
Respir Med ; 85(6): 517-20, 1991 Nov.
Article in English | MEDLINE | ID: mdl-1837931

ABSTRACT

The aim of the study was to determine the maximum effective dose of nebulized ipratropium bromide, 0.5 or 1.0 mg, in the treatment of acute severe attacks of asthma. Thirty-two patients (ten males, 19-53 years) who were admitted with acute severe asthma were, in a double-blind trial, randomized to receive either 0.5 or 1.0 mg of isotonic, preservative-free ipratropium bromide nebulized in saline. Ear oxygen saturation, peak flow and heart rate were measured on admission and regularly following nebulization. Two hours after nebulization of the ipratropium, terbutaline (5 mg) was administered by nebulizer and further measurements taken 30 min later. Twenty-six patients completed the study, 13 in each group. Peak expiratory flow (PEF) increased by 51% [1211 min-1 increasing to 1831 min-1 (mean)] in the 0.5-mg ipratropium group, and by 37% (1551 min-1 to 2071 min-1) in the 1.0-mg group. There were no significant differences in heart rate or ear oxygen saturation changes between the groups. Nebulized terbutaline led to a small further rise in peak flow in both groups (341 min-1 in the 0.5-mg group; 411 min-1 in the 1.0-mg group). No side-effects were noticed in either group. We conclude that 0.5 mg of nebulized ipratropium is as effective as 1.0 mg in the treatment of acute severe asthma.


Subject(s)
Asthma/drug therapy , Ipratropium/administration & dosage , Acute Disease , Administration, Inhalation , Adult , Asthma/physiopathology , Double-Blind Method , Drug Administration Schedule , Female , Humans , Lung/physiopathology , Male , Middle Aged , Nebulizers and Vaporizers , Peak Expiratory Flow Rate/drug effects , Terbutaline/therapeutic use
6.
Eur Respir J ; 4(2): 141-6, 1991 Feb.
Article in English | MEDLINE | ID: mdl-2044729

ABSTRACT

We studied 80 subjects (63 M, 17 F; 23-82 yrs) and related lung computerized tomography (CT) density with age, height, spirometry, lung volumes, diffusing capacity and arterial blood gas tensions. These subjects demonstrated a wide range of physiological impairment (forced expiratory volume in one second (FEV1) 8-116% predicted; diffusing capacity (Kco) 15-139% predicted; arterial oxygen tension (Pao2) 38-91 mmHg). They ranged from normal subjects to patients with chronic respiratory failure. Lung density was derived from CT density histograms measured as both mean Emergency Medical Information (EMI) number (EMI scale: 0 = water, -500 = air, EMI number of normal lung tissue range approximately -200 to -450) and the lowest 5th percentile EMI number, the latter value being more likely to represent the density of lung parenchyma. Lung CT density correlated most strongly with airflow obstruction (EMI 5th percentile versus FEV1/forced vital capacity (FVC) % predicted, r = 0.73, p less than 0.001) and diffusing capacity (EMI 5th percentile versus Kco, r = 0.77, p less than 0.001). This suggests that reduction in lung density, which reflects loss of the surface area of the distal airspaces, is a major index of respiratory function in patients with smoking related chronic obstructive pulmonary disease (COPD). These data provide no indication of other factors such as small and large airways disease, and loss of elastic recoil, which may contribute to airflow limitation, or disruption of the pulmonary vascular bed which may also affect CT lung density.


Subject(s)
Lung/diagnostic imaging , Pulmonary Diffusing Capacity , Pulmonary Emphysema/diagnostic imaging , Pulmonary Ventilation , Adult , Aged , Aged, 80 and over , Female , Humans , Lung/physiology , Male , Middle Aged , Pulmonary Emphysema/physiopathology , Tomography, X-Ray Computed
7.
Thorax ; 46(1): 39-42, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1871695

ABSTRACT

N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung.


Subject(s)
Acetylcysteine/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Cysteine/blood , Glutathione/blood , Acetylcysteine/administration & dosage , Administration, Oral , Adult , Aged , Cysteine/analysis , Female , Glutathione/analysis , Humans , Male , Middle Aged
9.
Eur Respir J Suppl ; 9: 5s-8s, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2340053

ABSTRACT

The definition of pulmonary emphysema is based on pathological examination. Clinical diagnosis is imprecise with no relationship between the extent of emphysema and either the "pink puffer" or the "blue bloater" types. The correlations between lung function tests and the extent of anatomically defined emphysema remain poor with a wide scatter. Plain chest radiograph is unreliable for the exclusion of emphysema whereas it is of value when positive. Major advance in the in vivo diagnosis has come from computed tomography (CT). It remains to be tested however whether serial quantitative CT scans will allow follow-up of the progression of emphysema.


Subject(s)
Pulmonary Emphysema/diagnosis , Forced Expiratory Volume , Humans , Lung/diagnostic imaging , Prognosis , Pulmonary Emphysema/diagnostic imaging , Pulmonary Emphysema/physiopathology , Smoking/adverse effects , Tomography, X-Ray Computed
10.
J Hum Hypertens ; 3(6): 419-25, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2575174

ABSTRACT

The treatment of systemic hypertension in patients with coexisting chronic airflow limitation is difficult. Even a 'cardioselective' beta-blocker potentially can increase airflow limitation. However it is very unlikely that alpha 1 blockers can bronchoconstrict. We have therefore evaluated the efficacy and safety of doxazosin, a new orally active selective alpha 1 blocker, in patients with systemic hypertension with concomitant airflow limitation. We studied 21 patients (11M, 10F) whose diastolic blood pressure was 95-114 mmHg and FEV1 22-73% of predicted. In the 19 patients who completed the study the dose of doxazosin to achieve satisfactory control of the systemic hypertension lay between 1 and 16 mg (mean 6 +/- 3.6 mg). This doxazosin dosage reduced the diastolic blood pressure on average from 103 to 91 mmHg (P = 0.0001). However this produced no significant changes in peak expiratory flow rate (PEFR) over the days of the study (P greater than 0.05). The mean variations in PEFR both 'day to day' (P less than 0.001) and 'within day' (P less than 0.002) were reduced during doxazosin therapy, and FEV1 rose on average from 1.6 to 1.7 (P less than 0.05). We conclude that doxazosin is an effective oral antihypertensive drug, which does not exacerbate pre-existing airflow limitation.


Subject(s)
Adrenergic alpha-Antagonists/therapeutic use , Asthma/complications , Hypertension/drug therapy , Lung Diseases, Obstructive/complications , Prazosin/analogs & derivatives , Pulmonary Ventilation/drug effects , Adult , Aged , Asthma/physiopathology , Blood Pressure/drug effects , Doxazosin , Female , Forced Expiratory Volume , Humans , Hypertension/complications , Lung Diseases, Obstructive/physiopathology , Male , Middle Aged , Peak Expiratory Flow Rate , Prazosin/therapeutic use , Prospective Studies , Respiration/drug effects , Single-Blind Method
11.
Clin Sci (Lond) ; 77(4): 431-7, 1989 Oct.
Article in English | MEDLINE | ID: mdl-2572372

ABSTRACT

1. In a double-blind placebo-controlled study, we have investigated the effect of the peripheral chemoreceptor stimulant drug almitrine bismesylate on hypoxic ventilatory drive (expressed as the slope of the minute ventilation/arterial oxygen saturation relationship in litres min-1+-1) as measured by both progressive isocapnic hypoxia at rest and transient hypoxia (three breaths of 100% N2) during moderate exercise, in seven normal men, to determine if the ventilatory response to the transient hypoxic stimulus is a more specific measure of peripheral chemoreceptor sensitivity to hypoxia. 2. Hypoxic ventilatory drive measured using progressive isocapnic hypoxia ranged from -0.13 to -2.65 litres min-1%-1 after placebo and from -0.20 to -6.48 litres min-1%-1 after almitrine. The response was greater after almitrine in six of the seven subjects, and the difference was significant for the whole group (P less than 0.05). 3. Hypoxic ventilatory drive measured using transient hypoxia ranged from -0.19 to -1.59 litres min-1%-1 after placebo and from -0.09 to -1.62 litres min-1%-1 after almitrine. The response was not consistently greater after almitrine, and the difference was not significant for the group. 4. Difficulties in accurately quantifying a brief rise in minute ventilation after transient hypoxia, particularly in subjects with a low hypoxic ventilatory drive, may have masked small changes in the slope of the minute ventilation/arterial oxygen saturation relationship with this method.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Almitrine/pharmacology , Central Nervous System Stimulants/pharmacology , Hypoxia/physiopathology , Respiration/drug effects , Adult , Double-Blind Method , Humans , Male , Physical Exertion
12.
Am Rev Respir Dis ; 139(6): 1509-15, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2729756

ABSTRACT

We have used the CT transthoracic scan to measure regional lung density in vivo, as our previous studies have shown that this correlates with the increase in size of distal air spaces, which is a defining characteristic of emphysema. We have studied 32 patients with chronic airflow limitation (FEV1, 15 to 68% predicted) caused by chronic bronchitis and emphysema (synonym, COPD), with a wide range of arterial PO2 (38 to 90 mm Hg) and PCO2 (32 to 63 mm Hg) while breathing air at rest. We could find no significant relationships between the extent of emphysema (as assessed in vivo by the EMI number defining the lowest fifth percentile of the CT density histogram of the lung fields) and either arterial blood gas tensions, mean pulmonary arterial pressure, cardiac output, or calculated total pulmonary vascular resistance while at rest (n = 32) or during supine leg exercise (n = 29). We conclude that the extent of emphysema does not correlate with the clinical or pathologic features of the "pink and puffing" (i.e., mild hypoxemia, no CO2 retention, no pulmonary hypertension, etc.) or "blue and bloated" (i.e., hypoxemia, CO2 retention, pulmonary hypertension) pattern of patients with COPD nor to the spectrum of hemodynamic and gas exchange abnormalities that commonly occur in patients between these two extreme examples. Thus, "pink puffers" should not be equated with "the emphysematous" pattern of this disease. Although these clinicophysiologic patterns remain valid as descriptions, they do not relate to the extent of underlying emphysema in COPD.


Subject(s)
Bronchitis/physiopathology , Lung/diagnostic imaging , Pulmonary Emphysema/physiopathology , Tomography, X-Ray Computed , Aged , Blood Pressure , Bronchitis/diagnostic imaging , Chronic Disease , Female , Humans , Male , Middle Aged , Pulmonary Artery/physiopathology , Pulmonary Emphysema/diagnostic imaging , Pulmonary Gas Exchange , Stroke Volume , Vascular Resistance
13.
Am Rev Respir Dis ; 139(2): 492-7, 1989 Feb.
Article in English | MEDLINE | ID: mdl-2563321

ABSTRACT

We studied the acute and long-term effect of the oral beta-2 agonist pirbuterol on pulmonary hemodynamics and right and left ventricular ejection fractions in 11 patients with stable hypoxic chronic bronchitis and emphysema who were maintained on long-term oxygen therapy. We have used a double-blind study with random allocation of patients to receive either pirbuterol or an identical-appearing placebo. Six patients received 15 mg pirbuterol thrice daily, and five patients received a similar placebo thrice daily, over a 6-month period. The first 15-mg dose of pirbuterol by mouth at the beginning of the study raised the heart rate from 84 +/- 13 to 100 +/- 16 beats/min (mean +/- SD) (p less than 0.01), and cardiac output from 5.2 +/- 0.9 to 6.4 +/- 0.8 L/min (p less than 0.01) and right ventricular ejection fraction (RVEF) from 0.28 +/- 0.10 to 0.33 +/- 0.12 (p less than 0.01) within 120 min after receiving the drug, but without significant change in the mean pulmonary arterial pressure. None of these variables changed significantly after an acute dose of placebo in another four patients. Repeated measurements after 6 months of chronic oral therapy with either pirbuterol or placebo showed that 16 h after the last 15-mg oral dose of pirbuterol or placebo, the heart rate, mean pulmonary arterial pressure, cardiac output, total pulmonary vascular resistance, and RVEF were all not significantly different from the values 6 months previously, before receiving either pirbuterol or the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Adrenergic beta-Agonists/administration & dosage , Bronchodilator Agents/administration & dosage , Ethanolamines/administration & dosage , Hypoxia/drug therapy , Oxygen Inhalation Therapy , Pulmonary Circulation/drug effects , Pulmonary Heart Disease/drug therapy , Aged , Chronic Disease , Combined Modality Therapy , Double-Blind Method , Drug Evaluation , Female , Hemodynamics/drug effects , Humans , Hypoxia/physiopathology , Male , Middle Aged , Pulmonary Heart Disease/physiopathology , Random Allocation , Stroke Volume/drug effects , Time Factors
14.
Respiration ; 55 Suppl 2: 4-9, 1989.
Article in English | MEDLINE | ID: mdl-2572039

ABSTRACT

Airflow limitation results from loss of elastic recoil (as in emphysema), or narrowing of large and small airways from smooth muscle contraction, mucosal swelling and/or oedema, mucous plugging (as in asthma), and loss of small airways (as in COPD). Bronchodilator regimes in asthma include inhaled beta 2-agonists, but these do not reduce bronchial hyper-reactivity but act quickly and synergise with oral slow-release theophyllines (serum level 10-20 micrograms/ml), without potentiating tremor which occurs with oral beta 2-agonists. Airway inflammation as the mechanism of asthma, although fashionable, remains unproven, and clearly requires to be specified for asthma. Inhaled steroids slowly improve FEV1 in asthma and in 10-20% of COPD, and reduce hyper-reactivity. Nedocromil has yet to reveal similar potency. Clinical trial of effective anti-PAF drugs or anti-leukotriene agents are awaited, but understanding the specific asthmatic inflammation is still needed for rational therapy. In COPD combining inhaled beta 2-agonists with ipratropium--both given by a reservoir device--can be effective, along with oral slow-release theophylline and possibly inhaled steroids. New inhalation devices (i.e. modified dry powder inhalers) will be needed as the freon propellents in MDI may soon cease manufacture due to potential environmental hazards.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Asthma/drug therapy , Bronchitis/drug therapy , Bronchodilator Agents/therapeutic use , Pulmonary Emphysema/drug therapy , Administration, Inhalation , Humans
15.
Chest ; 95(1): 65-70, 1989 Jan.
Article in English | MEDLINE | ID: mdl-2642413

ABSTRACT

The effect of histamine or methacholine inhalational challenge on breathing patterns and oxygen saturation was investigated in ten stable asthmatic patients. We used the respiratory inductive plethysmograph to record respiratory timing and minute ventilation along with an ear oximeter to measure oxygen saturation (SaO2). As FEV1 fell during the challenge procedure, SaO2 also fell (average 3 percent). Furthermore, with histamine challenge, expiratory time (Te), inspiratory time (Ti), and breath period (Ttot) all increased; minute ventilation probably also fell. These changes in breathing pattern and SaO2 were reversed by inhalation of a beta 2-agonist. However, no such changes in breathing patterns were observed with methacholine challenge despite a similar fall in FEV1. Bronchial challenge produces hypoxia in stable asthmatic patients, which might result from a combination of hypoventilation with alteration in alveolar ventilation/perfusion relationships.


Subject(s)
Asthma/physiopathology , Bronchial Provocation Tests , Oxygen/blood , Respiration/drug effects , Adolescent , Adult , Asthma/blood , Forced Expiratory Volume , Histamine , Humans , Male , Methacholine Chloride , Methacholine Compounds , Middle Aged
16.
Chest ; 94(6): 1169-75, 1988 Dec.
Article in English | MEDLINE | ID: mdl-3191757

ABSTRACT

In 100 patients with chronic obstructive pulmonary disease (COPD), we found no significant correlation between simultaneous measurements of right ventricular ejection fraction, using radionuclide ventriculography, and pulmonary arterial pressure. There was, however, a weak but significant correlation between right ventricular ejection fraction and the pulmonary vascular resistance (r = 0.40, p less than 0.005). In 52 of these patients, 37 with pulmonary hypertension, right ventricular end-systolic volume index was 53 +/- 21 ml.m-2 and end-diastolic volume index was 86 +/- 27 ml.m-2, compared with a calculated mean of 33 ml.m-2 and 79 ml.m-2, respectively, for normal subjects. In 24 of these patients where the measurements were made at rest and on exercise, the mean right ventricular end-systolic volume increased from 66 +/- 20 ml.m-2 to 87 +/- 32 ml.m-2, with an increase in right ventricular systolic pressure from 28 +/- 9 mm Hg to 55 +/- 15 mm Hg. Analysis of the slope of the right ventricular end-systolic pressure volume relationship at rest and on exercise suggested relatively normal right ventricular contractility in the majority of patients. Thus, in these patients with stable COPD, despite the presence of pulmonary hypertension, right ventricular contractility remained relatively normal.


Subject(s)
Heart/physiopathology , Hypertension, Pulmonary/physiopathology , Lung Diseases, Obstructive/physiopathology , Myocardial Contraction , Blood Pressure , Catheterization, Swan-Ganz , Female , Heart/diagnostic imaging , Humans , Male , Middle Aged , Pulmonary Artery , Pulmonary Heart Disease/physiopathology , Radionuclide Imaging , Stroke Volume , Vascular Resistance
17.
Dis Mon ; 34(9): 537-99, 1988 Sep.
Article in English | MEDLINE | ID: mdl-3048940

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is equated with chronic bronchitis and emphysema as one disease entity. In COPD airflow limitation is relatively persistent--unlike asthma. Tests for "small-airways disease" form no part of routine practice, for their accuracy in detecting pathological change is debatable. The proteolytic theory of the pathogenesis of emphysema highlights the role of neutrophil elastase, antielastases, oxidants, antioxidants, and thus of potential new treatments. Clinical features of COPD include breathlessness, cough, and sputum, with airflow obstruction and lung hyperinflation. The differential diagnosis includes bronchiectasis, cystic fibrosis, and pulmonary hypertension, but pulmonary fibrosis, etc., is distinguished by radiological infiltrates. Plain chest radiography cannot reliably diagnose emphysema in life, but a new method measuring lung density from the computed tomographic (CT) scan allows location, quantitation, and diagnosis of emphysema (defined by enlargement of distal air spaces) in humans in life. "Pink puffers" with breathlessness, hyperinflation, mild hypoxemia, and a low PCO2 are contrasted with "blue bloaters" with hypoxemia, secondary polycythemia, CO2 retention, and pulmonary hypertension and cor pulmonale. Antismoking measures are a major aim in management. A bronchodilator regimen combining a slow-release oral theophylline with an inhaled beta 2-agonist, ipratropium, and high-dose inhaled steroids is proposed because even modest improvement in obstruction can help these patients. In acute exacerbations with purulent sputum, antimicrobials against Streptococcus pneumoniae and Hemophilus influenzae are used with controlled oxygen therapy aiming to keep the arterial PO2 over 50 mm Hg without the pH falling below 7.25. Influenza prophylaxis is recommended, but pneumococcal vaccination remains debatable. Chronic under-nutrition in "emphysema" implies controlled trials of feeding regimens--but these remain to be assessed. Long-term oxygen therapy is the only treatment known to prolong life in blue bloaters, and oxygen concentrators and transtracheal oxygen delivery are discussed. Pulmonary vasodilators (e.g., beta 2-agonists, hydralazine, nifedipine, angiotensin-converting enzyme [ACE] inhibitors, etc.) have not yet been proved to provide long-term reduction in pulmonary arterial pressure. Blue bloaters have severe nocturnal hypoxemia in rapid eye movement (REM) sleep that is corrected by oxygen or the investigational drug almitrine.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Lung Diseases, Obstructive/diagnosis , Lung Diseases, Obstructive/therapy , Humans , Lung Diseases, Obstructive/etiology , Lung Diseases, Obstructive/physiopathology , Respiratory Muscles/physiopathology , Sleep/physiology
18.
Am Rev Respir Dis ; 137(6): 1289-95, 1988 Jun.
Article in English | MEDLINE | ID: mdl-3202369

ABSTRACT

We made simultaneous measurements of pulmonary hemodynamics, cardiac output, and right ventricular ejection fraction (RVEF) to assess the right ventricular function in 14 patients with pulmonary arterial hypertension as a result of chronic obstructive pulmonary disease (COPD). From these measurements, the right ventricular end-systolic pressure/volume relationship could be calculated and used to assess right ventricular contractility. Eight of the patients were clinically stable, without edema, and 6 presented acutely with gross edema, indicating decompensated cor pulmonale. Measurements were made at rest, while breathing air and oxygen. Although mean pulmonary arterial pressure (Ppa) was similar in those with (Ppa = 33 +/- 6 mm Hg) and without edema (Ppa = 30 +/- 8 mm Hg, p greater than 0.05), RVEF was lower in edematous (RVEF = 0.23 +/- 0.11) compared with non-edematous patients (RVEF = 0.47 +/- 0.04, p less than 0.01). Cardiac output was normal in both groups. The mean right ventricular end-systolic pressure/volume ratio (P/V) was lower in those patients with edema (P/V = 0.41 +/- 0.27), as compared with those without edema (P/V = 1.69 +/- 0.35, p less than 0.05), as a result of an increase in right ventricular end-systolic volume index. Similarly, left ventricular end-systolic volumes were higher in edematous than in non-edematous patients. Breathing 1 to 3 L/min of oxygen for 30 min decreased total pulmonary vascular resistance (p less than 0.05) in those patients without edema, but not in patients with edema. Oxygen did not change RVEF, left ventricular ejection fraction (LVEF), or the ventricular end-systolic P/V relationships.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Heart/physiopathology , Oxygen/therapeutic use , Pulmonary Heart Disease/drug therapy , Acute Disease , Cardiac Output , Heart Ventricles , Hemodynamics , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/physiopathology , Hypoxia/complications , Hypoxia/drug therapy , Hypoxia/physiopathology , Lung Diseases, Obstructive/complications , Lung Diseases, Obstructive/drug therapy , Lung Diseases, Obstructive/physiopathology , Pulmonary Circulation , Pulmonary Edema/complications , Pulmonary Edema/drug therapy , Pulmonary Edema/physiopathology , Pulmonary Heart Disease/physiopathology , Stroke Volume
20.
Am Rev Respir Dis ; 137(2): 380-92, 1988 Feb.
Article in English | MEDLINE | ID: mdl-3341629

ABSTRACT

We used a computerized microscopic image analysis system to directly measure the surface area of distal air spaces in methacrylate-embedded blocks randomly selected from inflation-fixed lobes that were resected from 45 patients as treatment of their peripheral lung tumors. In 28 of these patients, a preoperative computer tomography (CT) scan, at 6 and 10 cm below the sternal notch, was used to generate frequency histograms of CT numbers (measured as EMI units), a measure of lung density, in pixels from the lung or lobe that was subsequently resected. A similar CT number histogram was also derived from the lateral two fifths of the area of lobe/lung that was to be resected. The EMI unit that defined the lowest fifth percentile of this latter histogram correlated (n = 28, r = -0.77, p less than 0.001) with the mean value of the surface area of the walls of distal airspaces per unit lung volume (AWUV) in the five 1 mm x 1 mm microscopic fields with the lowest AWUV values, out of the 20 to 35 such fields examined in each patient. In the 34 of the 45 patients in whom we also measured volume-corrected diffusing capacity (DLCO/VA), this also correlated (n = 34, r = 0.84, p less than 0.001) with this value of AWUV, which measures the surface area of airspaces distal to the terminal bronchioles--reflecting an increase in airspace size, a defining characteristic of emphysema. However, a low DLCO/VA is nonspecific, whereas an abnormally low regional lung density is more likely to be specific for emphysema. In addition, highlighting those pixels of the CT display with low CT numbers (i.e., EMI units -500 [air] to -450, where zero = water) can locate areas of macroscopic emphysema, as shown by subsequent pathologic examination. Thus the quantitative CT scan can diagnose, quantitate, and locate mild to moderate emphysema, in humans, in life, noninvasively.


Subject(s)
Lung/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Tomography, X-Ray Computed , Aged , Female , Humans , Lung/physiopathology , Male , Middle Aged , Pneumonectomy , Preoperative Care , Pulmonary Emphysema/physiopathology , Pulmonary Emphysema/surgery , Respiratory Function Tests , Tomography, X-Ray Computed/methods
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