W.N. Gardner

CONTROLLED STUDY OF RESPIRATORY RESPONSES DURING PROLONGED MEASUREMENT IN PATIENTS WITH CHRONIC HYPERVENTILATION

The respiratory responses of 17 patients with chronic hyperventilation but without demonstrable organic disease (group H) to various manoeuvres were compared with those of 21 healthy controls (group C). The responses were tested according to a 60 min protocol in which periods of rest were replaced by exercise, voluntary hyperventilation (VHV), reading, and CO2 inhalation. 5 patients with severe resting hypocapnia were investigated overnight during sleep. Chronic hyperventilation was of two types--persistent or provoked by exercise or VHV. It was due to modest increases in tidal volume and respiratory frequency but was generally not conspicuous. End-tidal PCO2 levels were gradually corrected to near normal during sleep but not by inhalation of CO2.

UNEXPLAINED BREATHLESSNESS AND PSYCHIATRIC MORBIDITY IN PATIENTS WITH NORMAL AND ABNORMAL CORONARY ARTERIES

Of 99 patients with chest pain undergoing coronary arteriography, 31 had normal coronary arteries, 15 slight disease, and 53 significant coronary obstruction. 28 (61%) of the 46 with haemodynamically insignificant disease and 12 (23%) of the 53 with significant obstruction had psychiatric morbidity, assessed by standard interview. 37 patients had several respiratory symptoms and signs not attributable to organic disease, designated unexplained breathing disorder (UBD). UBD was found in 65% of the patients without and 13% of those with significant coronary disease; it was associated with psychiatric morbidity in the former but not in the latter group. Spirographic measurements of tidal volume and frequency were not helpful in detecting UBD but an end-tidal pCO2 below 30 mm Hg was highly suggestive. In the absence of significant coronary disease the associations of chest pain with psychiatric morbidity and UBD are striking. However, coronary disease and UBD are not mutually exclusive, and diagnostic difficulties can occur when they coexist.

Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non‐diabetic chronic renal failure

Aims An erythropoietin (EPO)‐deficient anaemia is recognized in Type 1 diabetic patients with early nephropathy and symptomatic autonomic neuropathy (DN). The aim of this study was to determine whether the EPO response to hypoxia was deficient in order to clarify the mechanisms involved in this process.

Hyperventilation and asymptomatic chronic asthma

BACKGROUND We have consistently argued that mild asthma is an important underlying aetiological factor in patients with severe symptomatic hyperventilation. While hyperventilation has been demonstrated in acute asthma, there have been few studies in mild chronic asthma, and mechanisms are uncertain. METHODS Twenty three currently asymptomatic chronically asthmatic patients (occasional use of bronchodilators, normal lung function, hyperresponsive to methacholine) were studied and 17 matched normal subjects acted as controls. Ventilation, pattern of breathing, arterial carbon dioxide and oxygen tensions (Paco 2, Pao 2), end tidal Pco 2(Petco 2), standard lung function, airway responsiveness to methacholine, airway inflammation assessed by eosinophils in induced sputum, and psychiatric morbidity (Spielberger STAI-Y and Beck Depression Inventory) were measured. RESULTS Despite the absence of current asthmatic symptoms, no clinical evidence of hyperventilation, and normal lung function in the patients with asthma, Paco 2 and Petco 2 were significantly (p<0.01) lower in the patients than in the control group (mean (SD) Paco 2 4.96 (0.43) kPa for patients versus 5.27 (0.38) kPa for controls (mean difference 0.31 kPa, 95% confidence interval (CI) 0.06 to 0.56, p<0.02)). Petco 2 was very similar to Paco 2 in both groups (mean (SD) Petco 2 4.89 (0.47) kPa for the patients and 5.28 (0.40) for the controls (mean difference 0.39 kPa, 95% CI 0.12 to 0.66, p<0.01)). There was no significant difference in ventilation or respiratory pattern between the two groups. The reduced Paco 2 in the asthmatic patients correlated significantly with the concentration of methacholine provoking a fall in FEV1 of more than 20% (PC20) (r = 0.56, p<0.01) but not with any aspect of lung function, eosinophil count, or anxiety/depression. CONCLUSION Mild asymptomatic asthma is not associated with clinically significant hyperventilation but is associated with a significant reduction in both arterial and end tidal Pco 2 which relates to airway hyperresponsiveness rather than to the degree of airway obstruction or mucosal inflammation. Anxiety and depression appear not to be implicated.

Value of measuring end tidal partial pressure of carbon dioxide as an adjunct to treadmill exercise testing

The end tidal partial pressure of carbon dioxide (Pco2) was measured during treadmill exercise in 30 normal controls and 113 patients referred for assessment of chest pain. Among the 92 patients without significant ST depression hypocapnia occurred more often in those reporting “typical” than “atypical” chest pain (17 of 22 patients compared with 29 of 70; p<0·01). Hypocapnia was uncommon in patients with significant ST depression whether reporting typical or atypical chest pain (one of 10 patients and two of 11, respectively). Hypocapnia at rest (Pco2 <4 kPa) occurred in 16 (14%) patients but in only one control. Hypocapnia occurred during or after exercise in only one control and three of the 21 patients with significant ST depression on exercise (group 1). The remaining 92 patients were divided into those with a history suggestive of hyperventilation (group 2; n=30) and those without (group 3; n=62). Hypocapnia developed significantly more often in both these groups (21 and 25 patients respectively) than in controls or patients with significant ST depression. An abnormal response of the Pco2 to exercise provided objective data to support a clinical suspicion of chest pain induced by hyperventilation in 24 cases, suggested a cause for equivocal ST depression other than coronary stenosis in five patients, and led to the diagnosis of previously unsuspected respiratory disease in 14 patients. Measurement of end tidal Pco2 gives additional valuable diagnostic information during the conventional treadmill exercise test in patients with both typical and atypical chest pain.

Pseudoseizures and asthma

Background: Sexual abuse and head injury are important risk factors of pseudoseizures, reported in about a third of patients. Clinical experience suggests that asthma is another possible risk factor. Objectives: To determine the relative prevalence of asthma in patients with pseudoseizures. Methods: A retrospective record review was undertaken of reported asthma in 102 patients with pseudoseizures and 70 psychotic controls. The pseudoseizure patients were subgrouped according to method of diagnosis: 47 in whom epilepsy was excluded by capturing a typical attack on video-electroencephalographic monitoring (VEEM), and 55 not diagnostically confirmed with VEEM. Results: Asthma was reported in 26.5% of pseudoseizure patients, compared with 8.6% of the psychotic controls (χ2 = 8.6; p = 0.003). Asthma was reported at similar rates in the VEEM confirmed (29.8%) and non-VEEM confirmed (23.6%) pseudoseizure subgroups. The significant excess of reported asthma held for both the VEEM confirmed subjects (Pearson’s χ2 = 5.4, p = 0.02) and non-VEEM confirmed subjects (Pearson’s χ2 = 8.9, p = 0.003). Conclusions: There is an association between pseudoseizures and reported asthma. Various models are proposed whereby somatisation, anxiety hyperventilation, and dissociative elaboration may account for the observed association. Both asthma and anxiety hyperventilation may be important risk factors for the development of pseudoseizures. The reported asthma may itself be psychogenic in origin in a proportion of patients. Confirmatory prospective studies are indicated.

HYPERVENTILATION PROVOCATION IN PATIENTS WITH CHEST PAIN AND A NEGATIVE TREADMILL EXERCISE TEST

Seventeen (39%) of 44 patients with chest pain but without significant ST depression on treadmill exercise had their usual chest pain reproduced during or after 3 min of voluntary hyperventilation (VHV) at rest. These patients with hyperventilation positive tests had not only significantly more hyperventilation-related symptoms and respiratory complaints but also shorter breath-holding times, lower mean resting end-tidal pCO2 and higher mean respiratory rates than those with negative tests and normal controls. Of the psychological variables, only phobic avoidance scores for agoraphobia were higher in patients with positive tests. These findings suggest that in two fifths of patients with exercise tests negative for ischaemia, chest pain is associated with HV, but abnormalities of breath control and relative hypocapnia are present even in the absence of chest pain. It is possible that a chronic abnormality of respiratory control may interact with attitudinal factors in the experience of non-cardiac chest pain.

Orthostatic increase of respiratory gas exchange in hyperventilation syndrome

The paper by Malmberg et al in the current issue of Thorax 1 deals with the difficult subject of the hyperventilation syndrome and finds that these patients have a disproportionately high ventilatory response to change of body position from supine to standing. The authors suggest that this can be used as a diagnostic criterion for hyperventilation syndrome. Hyperventilation is a confused and poorly documented subject and the publication of this paper provides an opportunity to review some of the particularly controversial aspects of this subject. The first issue concerns the basis for the labelling of these patients as “hyperventilation syndrome”. Some of the controversies about the use of this term have recently been reviewed by Folgering2and by Gardner.3 The physiological definition of hyperventilation is alveolar ventilation that is inappropriately high for the metabolic production of carbon dioxide, leading to reduction of arterial Pco2 (Paco 2) below the normal range (hypocapnia) and respiratory alkalosis. The combination can lead both to vasoconstriction in selected vascular beds and to neuronal hyperexcitability producing symptoms involving most systems of the body. Many psychosomatic syndromes have been described in the past in which hyperventilation has a variable and uncertain role but the term “hyperventilation syndrome” was first used in 1938 to describe patients with the somatic symptoms of both hypocapnia and anxiety.4 This theme was extended by subsequent authors5-7 and the definition arrived at by Lewis and Howell in 1986 on the basis of a questionnaire of delegates at a psychophysiology meeting8 was “a syndrome induced by physiologically inappropriate hyperventilation and usually reproduced in whole or in part by voluntary hyperventilation”. However, the term “hyperventilation syndrome” is now used in so many different contexts that it could be argued that it has ceased to have any universal meaning. …