The paper by Jack and coworkers in the current issue of the Journal (pp. 118–125) describes aspects of control of breathing in a group of patients with idiopathic hyperventilation (1). Hyperventilation involves medicine, physiology, psychology, and psychiatry, although it has failed to attain legitimacy in any of these specialties. The subject has been recently reviewed (2–4). There is still widespread misunderstanding about the implications of the finding of a low arterial (PaCO2) or end-tidal (PetCO2) carbon dioxide tension, and most physicians still use it as a euphemism for an anxiety state or psychosomatic disorder. This is not necessarily correct and unfairly labels patients as “psychiatric.” Most literature on this subject is very old and good papers using modern technology are sparse. The difficulty with this subject is clarifying the issues that need to be addressed, and there has in the past been little consensus. All working in this field have their own set of beliefs and this editorial will be no exception.
The first issue in the study of Jack and coworkers (1) concerns the etiology of the excessive respiratory drive causing the hyperventilation. Are we dealing with a unified group of patients? Is hyperventilation a disorder per se or is it a clinical finding equivalent to a low potassium for which a cause should be sought? Unfortunately, in the present study few details are given as to how individual patients presented, although they were recruited from chest clinics and thus must have been symptomatic. There are a number of possibilities.
Although only described anecdotally (3), there are patients well known to every chest clinic who present with breathlessness and “air hunger” of unknown etiology in whom hyperventilation is probably an epiphenomenon secondary to the breathlessness or the cause of the breathlessness. Hyperventilation is not necessarily associated with breathlessness and PetCO2 can be halved with only a 10% increase in ventilation (5). In these patients, breathlessness and not hyperventilation is the problem and until the cause of the breathlessness can be elucidated caution should be used in regarding these patients as having primary hyperventilation. Unfortunately, the basic mechanisms of breathlessness are still poorly understood.
Asthma, especially when mild and atypical, is a potent cause of hyperventilation (6). We previously found that 80% of patients presenting to an emergency department with apparent pure acute hyperventilation had good evidence of asthma that was previously undiagnosed in half (7). Chest tightness is not a symptom of hyperventilation per se. The suggestion in the study of Jack and coworkers that some patients had chest tightness suggests that some may have been asthmatic. By definition, lung function is normal in asthma after treatment and in my view additional investigations such as bronchial challenge tests, ambulatory peak flow recordings, or a trial of inhaled steroids are desirable to ensure exclusion of atypical asthma.
A third possibility is that some of these patients fall into a group, which we described in 1986, where intractable chronic hyperventilation is associated with a range of vague symptoms but especially chest pain (5, 8). These patients had persistent hyperventilation at rest and during exercise, but PetCO2 slowly returned back to normal during sleep. All had air hunger, some were phobic, but anxiety was not common.
A fourth possibility is that these patients in fact have no abnormalities at all but are at one end of the spectrum of the normal range of resting PaCO2. That this is possible was shown in a very carefully controlled and validated study (9, 10) in which we measured PetCO2 by an ambulatory capnograph in a group of normal subjects during four hours of activities of daily living including eating, talking, and mild exercise. The upper limit of normal for induction of hypocapnic symptoms in normal subjects is 28 mm Hg (11), and a significant percentage of our normal subjects had PetCO2 levels near or below this value for at least part of the time studied.
Does the etiology of the hyperventilation matter in respect to the study of Jack and coworkers? I believe it does. Lung function tests were all normal in this study but are fairly crude measures of lung mechanics. Control of breathing, especially in the hypocapnic range, may be influenced by subtle factors that are very different in each of the above conditions and the etiology of hyperventilation is almost certainly multifactorial in many patients. Despite these uncertainties about etiology, it is gratifying that the authors have accepted the growing consensus that the old nomenclature of “hyperventilation syndrome” should be abandoned because there has been complete failure of agreement as to how this syndrome should be defined or whether it even exists.
The present study contains carefully documented and standardized data showing that carbon dioxide and hypoxic sensitivities are near normal in these patients. This is not surprising. Hyperventilation probably induces a small shift of the CO2 response curve leftward to lower levels of PaetCO2 (12) (this requires further study in patients with hyperventilation). The PaetCO2 levels in the patients in the present study are almost certainly well down in the “dogleg” region of the CO2 response curve, where the central and probably peripheral chemoreceptors are inactivated and where all respiratory drives are feedforeward drives from the cortex and other sites (13). It is difficult to see how increase or decrease in chemoreceptor sensitivity could have any impact on the resting PaetCO2 level in these patients. The presence of persistent hyperventilation and increased breathlessness during exercise makes a convincing case that the additional respiratory drive in these patients is not of cortical origin, and the emphasis in the future must be in elucidating the basis of this additional drive.
Whatever the deficiencies of the study, it is gratifying to see a serious attempt to study this difficult subject that is a bane of the life of most chest physicians.
| 1. | Jack S, Rossiter HB, Pearson MG, Ward SA, Warburton CJ, Whipp BJ. Ventilatory responses to inhaled carbon dioxide, hypoxia and exercise in idiopathic hyperventilation. Am J Respir Crit Care Med 2004;170:118–125. |
| 2. | Folgering H. The hyperventilation syndrome. In: Altose MD, Kawakami Y, editors. Control of Breathing in Health and Disease. New York & Basel: Marcel Dekker Inc.; 1999. p. 633–660. |
| 3. | Gardner WN. The pathophysiology of hyperventilation disorders. Chest 1996;109:516–534. |
| 4. | Lum LC. Hyperventilation syndromes in medicine and psychiatry: a review. J R Soc Med 1987;80:229–231. |
| 5. | Gardner WN, Meah MS, Bass C. Controlled study of respiratory responses during prolonged measurement in patients with chronic hyperventilation. Lancet 1986;ii:826–830. |
| 6. | Osborne CA, O'Connor BA, Lewis A, Kanabar V, Gardner WN. Hyperventilation and asymptomatic chronic asthma. Thorax 2000;55:1016–1022. |
| 7. | Saisch SGN, Wessely S, Gardner WN. Patients with acute hyperventilation presenting to an inner-city emergency department. Chest 1996;110:952–957. |
| 8. | Bass C, Gardner WN. Respiratory and psychiatric abnormalities in chronic symptomatic hyperventilation. BMJ 1985;290:1387–1390. |
| 9. | Osborne CA, Varley JS, Gardner WN. Computerized editing of end-tidal PCO2 for ambulatory capnography [abstract]. Am J Respir Crit Care Med 2001;153:A919. |
| 10. | Osborne CA, Varley JS, Gardner WN. The true range of end-tidal PCO2 in normal humans measured uninvasively over 4 hr during activities of daily living. J Physiol 2001;531:44P. |
| 11. | Rafferty GF, Saisch SGN, Gardner WN. Relation of hypocapnic symptoms to rate of fall of end-tidal Pco2 in normal subjects. Respir Med 1992;86:335–340. |
| 12. | Cunningham DJC. Integrative aspects of the regulation of breathing. In: Guyton, Widdicombe JG, editors. Respiratory Physiology. London: Butterworths; 1974. p. 303–370. |
| 13. | Meah MS, Gardner WN. Post-hyperventilation apnoea in conscious humans. J Physiol 1994;477:527–538. |
