Severe Pulmonary Dysfunction Research Articles

Hospital therapy improves exercise tolerance and lung function in cystic fibrosis.

We studied the benefits of in-hospital therapy on exercise capacity and related these changes to improvements in lung function in 17 patients with cystic fibrosis (CF) of moderate to extreme severity, as defined by results of pulmonary function tests performed at admission and discharge. Tolerance and adaptations to exercise were assessed from measures of peak work capacity (PWC), peak heart rate (PHR), and peak ventilation (PVE) obtained during an incremental exercise test. Treatment lasted from nine to 18 days. All measures of lung function improved; there also were significant increases in PWC, PHR, PVE, and PHR/PWC. Exercise-induced arterial desaturation was less at discharge than at admission. The PWC of the most severely affected patients remained abnormally low, and their adaptations to exercise were abnormal at discharge. We concluded that intensive in-hospital therapy will significantly improve exercise tolerance and lung function in patients with CF with moderate to severe pulmonary dysfunction.

Cardiovascular function in patients with progressive systemic sclerosis (scleroderma).

Sixteen patients with progressive systemic sclerosis (PSS), including 3 with the "CREST" (calcinosis, Raynaud's, esophageal dysfunction, sclerodactyly, and/or telangiectasias) variant, were evaluated with resting M-mode echocardiography and noninvasive measurements of cardiac output at rest and during submaximal exercise to determine the nature and extent of any cardiovascular impairment. No patient had arterial hypertension, significant renal impairment, clinical evidence of large vessel coronary artery disease, or severe pulmonary dysfunction. The duration of disease was 1 to 12 years (9 to 30 for patients with the CREST variant). Echocardiographic abnormalities included increased right ventricular dimension (3 patients), reduced left ventricular ejection fraction (3 patients), and pericardial effusion (3 patients). Cardiac index (CI) and stroke volume index (SVI) at rest were similar for patients and controls. Patients and controls were exercised to similar heart rates (130 +/- 3 vs 124 +/- 4; p, NS). Total peripheral resistance (TPR) was higher for patients (1123 +/- 81 vs 810 +/- 44 dyn X s X cm-5) and their mean SVI failed to increase significantly compared with sitting rest values (30 +/- 2 vs 35 +/- 3 ml/m2). The control subjects had the expected increase in SVI (36 +/- 2 vs 51 +/- 5; p less than 0.01). Ten patients with an abnormal hemodynamic response to exercise had a normal echocardiographic circumferential fiber shortening (VCF) or ejection fraction (EF) at rest. The data indicate that PSS patients have a greater degree of cardiovascular dysfunction than would be predicted from clinical data and laboratory evaluation of cardiovascular and pulmonary function at rest. Multiple mechanisms, including right and left ventricular dysfunction and abnormal vasoconstrictor activity, are likely to contribute to the reduction in exercise capacity seen in patients with PSS.

Abnormal colonic motility in progressive systemic sclerosis.

Progressive systemic sclerosis alters smooth muscle function throughout the gastrointestinal tract. In 10 consecutive patients with the disease, colonic spike activity and contractile activity were measured after a 1000-kcal meal, intramuscular injection of neostigmine, or intravenous injection of metoclopramide. The 1000-kcal meal stimulated a significant increase in spike and contractile activity in normal subjects. Nine of the 10 patients had no increase in motility after eating. Neostigmine or metoclopramide stimulated colonic spike (p less than 0.01) and contractile (p less than 0.02) activity in normal subjects and stimulated colonic motility (p less than 0.01) in four of 10 patients with less severe systemic manifestations of the disease (Group 1). The drugs had no effect on patients with severe progressive systemic sclerosis (Group II). The patients with severe scleroderma had significant gastrointestinal roentgenographic abnormalities and severe cardiac, renal, or pulmonary dysfunction. Four of six Group II patients died from the disease; all four had marked smooth muscle atrophy in the colonic wall. These findings suggest that the gastrocolonic response is absent early in the disease process and that the smooth muscle atrophy occurring with progression of the disease may lead to a more severe colonic motor disturbance.

871 ACYCLOVIR THERAPY OF PRIMARY VARICELLA IN LEUKEMIA

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is an acyclic nucleoside analogue with in vitro activity against herpesviruses including varicella-zoster virus. Acyclovir has had little toxicity except for occasional bullae secondary to drug extravasation. We report our uncontrolled experience with this agent in four children with acute lymphocytic leukemia in remission and disseminated primary varicella with involvement of liver, lungs, CNS, and evidence of myelosuppression and coagulopathy. Progressive organ dissemination of varicella was present in each patient, with new skin lesions in 2, despite three daily infusions of adenine arabinoside (Ara-A). Ara-A was discontinued and IV acyclovir begun at the dose of 500 mg/M2 every 8 hours. Clinical improvement beginning within 24 hours of initiation of acyclovir with subsequent complete recovery following 7-10 days of drug occurred in 3 of 4 patients. The remaining patient, who manifested the most severe CNS, hepatic, and pulmonary dysfunction, ceased developing new skin lesions after acyclovir was begun but showed continued CNS and pulmonary deterioration with DIC, and died after three days. We observed no toxicity except for cutaneous bullae in one patient. This experience suggests that acyclovir may play a role in the treatment of disseminated primary varicella in immunocompromised hosts. Further controlled therapeutic trials with this agent are indicated.

Selective use of ventilator therapy in flail chest injury

We have prospectively treated 36 patients with flail chest using a treatment protocol for limited use of mechanical ventilation. Age of the patients ranged from 6 months to 83 years. Patients were divided into three groups dependent upon their clinical presentation and need for respiratory support: Group I patients had severe pulmonary dysfunction-tachypnea, dyspnea, arterial PO2 less than or equal to 60 torr, arterial PCO2 greater than or equal to 50 torr or shunt fraction greater than or equal to 25%. Group II patients had no pulmonary dysfunction but did require temporary respirator support for an associated injury. Group III patients had no pulmonary dysfunction. Thirteen patients were assigned to Group I. They required respiratory support for an average of 10.5 days; 11 of the 13 had complications, and there were two deaths in this group resulting from a combination of respiratory failure and myocardial infarction. Seven patients were assigned to Group II. six patients were extubated immediately postoperatively; one patient with a head injury was hyperventilated for 48 hours to reduce intracranial pressure and then extubated. Sixteen patients were assigned to Group III. Fifteen required no ventilatory support. One 83-year-old man developed pneumonia and was mechanically ventilated for 31 days. Early effective pain control and chest physiotherapy were critical to success and were used in all patients. Increase in respiratory rate, fall in tidal volume or vital capacity, and increased pain were used as criteria for administration of analgesia. Nonventilatory therapy of flail chest reduces morbidity, mortality, and hospital cost.

'The Shrinking Man'-Reply

In Reply.— Dr Lindsey is correct in his statement that a second exploration for recurrent hyperparathyroidism should never be undertaken without venous sampling for parathyroid hormone assays. However, when our patient underwent his second exploration in 1975, the technique of venous sampling was not available to us. Since that time the severe kyphoscoliosis with severe pulmonary dysfunction have prevented further intervention. This patient is an extreme example of renal osteodystrophy, which, because of the length of time he has been receiving hemodialysis, has produced this picture.

GENERALIZED EXTENSIVE IDIOPATHIC PULMONARY OSSIFICATON IN A DOG: A CASE REPORT

A 9‐year‐old dog was presented with generalized extensive pulmonary mineralization associated with exertional dyspnea and cyanosis. The differential diagnosis for the pulmonary mineralization included metastaticand dystrophic pulmonary calcification, atypical pulmonary neoplasia, alveolar microlithiasis, idiopathic pulmonary mineralization, and idiopathic pulmonary ossification. The dog was euthanized at the owner's request. The histologic diagnosis was idiopathic pulmonary ossification. No previous report of generalized extensive idiopathic pulmonary ossification was found. Idiopathic pulmonary ossification occurs in man, usually involves a limited area of lung, and is functionally unimportant. The pulmonary ossification in the dog reported here was generalized and associated with severe pulmonary dysfunction. The disease in man and that in the dog in this report do not appear to be directly comparable.

Septic Lung and Shock Lung in Man

Two series of patients were studied by serial measurements of blood gas exchange and pulmonarmonary dysfunction and to evaluate the dangers of respiratory failure in post traumatic patients. There were 27 patients who had sustained profound hemorrhagic shock and massive blood replacement averaging 9.7 liters and 38 patients who suffered general peritonitis or other forms of fulminating nonthoracic sepsis. All were supported by endotrachael intubation and volume controlled ventilators. The overall mortality for the post shock patients without sepsis was 12% while in the septic patients it was 35%. The maximal pulmonary arteriovenous shunt encountered in the post hemorrhagic shock patients at 36 hours averaged 20 plus or minus 8% and was accompanied by high cardiac indices (average 5.1 plus or minus 1.3 L/M-2/min) but no significant rise of pulmonary arterial pressure or peak inspiratory pressure (PIP). Severe pulmonary dysfunction subsequently occurred only in those patients who later became septic. The studies on the septic patients were divided according to the magnitude of the cardiac indices (the high indices averaged 4.8 plus or minus 1.6L/M-2/min) and thelow indices averaged 1.9 plus or minus 1.0 L/M-2/min. In the former, the average maximal shunt of 30 plus or minus 6% was sustained for 4 or more days, accompanied by an elevation of PIP to 36 plus or minus 6 cm H2O and by Pa pressure of 28 plus or minus 5 mm Hg. The patients in low output septic shock usually had an associated bronchopneumonia and had an average venous admixture of 34 plus or minus 8% and PIP values of 41 plus or minus 8 cm H2O. The mean Pa pressure in this group was 29 plus or minus 6 mm Hg.

ELECTROENCEPHALOGRAMS OF PATIENTS WITH CYSTIC FIBROSIS.

In 1961, Greutzner and Geletneky1reported a high incidence of abnormal electroencephalograms in adult and pediatric patients with cystic fibrosis. Their study also revealed a correspondingly high incidence among the relatives of these patients. In addition, abnormal slowing in brain wave frequency occurred in 50% of the patients with elevated sweat chloride and sodium concentrations. Their findings suggested central nervous system involvement to be a systemic manifestation of the disease, and it was postulated that this involvement was secondary either to a primary genetic defect or to a metabolic disturbance. Approximately 95% of all patients with cystic fibrosis of the pancreas manifest pulmonary symptoms which may result in severe pulmonary dysfunction with pulmonary insufficiency and respiratory acidosis. Since it is known that pulmonary insufficiency can contribute to hypoxia as well as to cerebral symptoms,2an attempt was made to investigate the relationship of the electroencephalograms to arterial