J. Bernard L. Gee

Combined central alveolar hypoventilation and upper airway obstruction. Treatment by tracheostomy and diaphragm pacing.

Abstract Long-term pacing of the diaphragm by electrical stimulation of the phrenic nerve has been successfully employed since 1966 in the treatment of patients with alveolar hypoventilation of central origin. Patients were selected for pacing on the basis of arterial blood gas levels indicating hypoventilation, abnormal ventilatory responses to hypercapnia and hypoxia, and characteristic clinical features. The coexistence of central alveolar hypoventilation and sleep-associated upper airway obstruction was detected in 14 patients. Recordings of several physiologic parameters were made during sleep to monitor changes in ventilatory function. Periodic apnea was observed in all patients. Three types were identified: apnea of central origin, that due to upper airway obstruction or a combination of the two. Pacemaker related apneas were also noted. Pacing the diaphragm eliminated apnea of central origin, accentuated apnea due to upper airway obstruction and, in two patients, both of whom had prolonged episodes of central apnea, pacing induced upper airway obstruction. Tracheostomy was performed for the relief of upper airway obstruction in 13 patients. Abnormal ventilatory responses to hypercapnia and hypoxia persisted in five of six patients studied. Of 12 patients studied after tracheostomy nine continued to show marked hypoventilation during sleep and three showed only mild hypoventilation; nocturnal pacing is being continued in these three patients to prevent a recurrence of alveolar hypoventilation. Our studies indicate that upper airway obstruction frequently accompanies central alveolar hypoventilation; the determination of their relative importance requires a ventilatory control study and a carefully monitored sleep study. In patients with combined central alveolar hypoventilation and upper airway obstruction whose condition is resistant to medical therapy, combined tracheostomy and diaphragm pacing are indicated.

The clinical assessment of roentgenographically atypical pulmonary sarcoidosis.

We studied 89 patients in whom the clinical diagnosis of sarcoidosis was supported by the findings on tissue biopsy. A chest roentgenogram in 14 of the patients showed one of the following atypical features: large pulmonary nodules, an alveolar parenchymal pattern or a pleural effusion. Diagnoses of infection, malignancy or vasculitis were suggested by interpretations of atypical chest roentgenograms in eight of these 14 patients. Nonspecific and misleading clinical information contributed. The diagnosis of sarcoidosis was corroborated by extrathoracic tissue biopsies in 11 of the 14 patients. Over an average observation period of 38 months, the 14 patients remained classified as having sarcoidosis. This suggests that an extrathoracic tissue biopsy, whose findings are consistent with sarcoidosis, is often sufficient to support a clinical diagnosis of some forms of roentgenographically atypical pulmonary sarcoidosis.

Sarcoidosis and mononuclear phagocytes.

Sarcoidosis is frequently associated with elevations of serum levels of either lysozyme or angiotensin-converting enzyme or both. Elevation of serum lysozyme probably derives from increased monocyte secretion of lysozyme and from increases in the lysozyme activity of the lung macrophage. Human alveolar macrophages from sarcoidosis patients contain more angiotensin-converting enzyme than normal human alveolar macrophages. The pathogenetic, diagnostic and therapeutic significance of these observations are discussed.

Linoleic Acid Hydroperoxide: Impaired Bacterial Uptake by Alveolar Macrophages, a Mechanism of Oxidant Lung Injury

Exogenous linoleic acid hydroperoxide causes in vitro impairment of both bacterial uptake and the phagocytic stimulation of 14CO2 production from [1-14C]glucose in rabbit alveolar macrophages by an undefined effect on the cell membrane. This effect may be one mechanism for the defective pulmonary bacterial clearance characteristic of oxidant lung injury.

Computerized tomography in pulmonary sarcoidosis.

Six patients with documented pulmonary sarcoidosis were selectively studied with the ACTA scanner. The CT scans were correlated with the standard chest radiographs of these patients. CT scans readily confirmed adenopathy, calcification, and pleural disease. Likewise, diffuse and isolated parenchymal disease was detected and in some cases unexpected lung involvement was noted.

Pulmonary granulomas in a patient with pulmonary veno-occlusive disease.

A patient with pulmonary veno-occlusive disease is described. Lung biopsy revealed noncaseating granulomas in conjunction with the typical vascular changes of this entity. This concurrence has not been previously described.

Asbestos-Related Pleural Plaques and Diffuse Pleural Thickening: Functional Consequences

Asbestos is associated with both pleural plaques and diffuse pleural thicken ing. While the first condition is believed to be associated with no significant change in lung function, the latter clearly is associated with a decline in lung function. Some of the studies dealing with the functional effects of pleural plaques suffer from radiologic misreading of plaques, inadequate spirometry and inadequate control for the effect of gain in weight on lung function.

Clinicians’ Approach to Mesothelioma

Prior to 1960, malignant mesothelioma (MM) was considered a rare and ill-defined entity of obscure etiology. The recognition of an origin from amphibole asbestos provided a case series of sufficient size both to characterize the tumor and to identify epidemiologically its commonest cause. Although MM is a relatively rare tumor (1), many clinicians become involved in the care of patients with, or at risk of, MM. Clinicians may play several roles, as summarized in Table 23.1. The scientific basis guiding approaches of clinicians is discussed throughout this book. In addition, the specific clinical manifestations of the common types of MM are presented in this chapter and Chapters 24 and 25.

Smoking and Occupational Lung Disease Epidemiology

Epidemiology studies of lung cancer which may be the result of workplace exposure contrast the risk ratios or SMRs of the exposed population with a control group. If a dose-response relationship can be detected then this suggests a causal relationship between the exposure and its effect. Smoking is clearly a substantial confounding factor but unfortunately adjustment for this is often limited by lack of accurate data. Most commonly only ‘ever’ versus ‘never’ smokers numbers are available and even then this data may only be available for some of the cohort. In the various studies of silica and lung cancer it is important that the smoking history of both silica-exposed and control groups is known. If the prevalence of smoking was similar in the two groups this would remove the confounding, but differences in the groups are usually present. Since the SMRs from a number of studies of silica and lung cancer are about 1.5 it is suggested that these might be close to smoking-adjusted SMRs. By contrast, where the SMR is >2.0, smoking adjustments are likely to affect the magnitude but not the statistical significance of the result.

Silica Induced Alveolar Leucocytosis: Modulation by Mepacrine

The initial response of the lung to inhalation of many dusts frequently includes the mobilization of polymorponuclear leucocytes (PMN) into the alveolar spaces. Lugano et al. (1982) demonstrated such a response following intra-tracheal instillation of silica particles in guinea pigs. The response occurred within the first 24 hours and was followed by fibrosis at the seventh post-instillation day. We used a somewhat similar model employing adult Fisher 344 rats which received 0.5 mg of autoclaved endotoxin free Minusil in 0.35 ml of saline by the intratracheal route-a full report is now published (Mikes, P.S., et al. 1988a). Briefly this model showed that broncho-alveolar lavage (BAL) fluid showed a twofold increase in cell yield, of which 35% were PMN. This contrasts with the 1% PMN yield in control animal BAL fluid. This represents a 200 fold increase in the number of lavage recovered PMN. The PMN response was not accompanied by much increase in either total protein or albumin concentration in the BAL fluid from silica treated animals, thus no great inflammatory response occurred at least as judged by this measure of capillary permeability.