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Cystic fibrosis, the most frequently seen lethal genetic syndrome, is now increasingly being recognized as a heterogeneous condition. Following a discussion of the many recognizable abnormalities that may be involved in the condition, this article examines the diagnosis, treatment, psychosocial care, and prognosis of cystic fibrosis and encourages greater dialogue between the pediatrician and the mental health consultant.

• Failure of the right side of the heart with cardiac dilation and fluid retention occurred in 55 of 170 patients who died of cystic fibrosis; six patients survive. All had severe hypoxia, but 24% had normal Paco2. Cardiac catheterization showed high mean pulmonary artery pressure and resistance. Pulmonary artery wedge pressure was greater than 12 mm Hg in 40% of the patients. Mean survival was eight months. Male survival was significantly better than female survival. Digitalis treatment was of no clear benefit. Tolazoline hydrochloride was also ineffective. Recent medical advances have not substantially affected prognosis.(Am J Dis Child 134:267-272, 1980)

We studied the clinical and laboratory characteristics of seven patients with sweat chloride concentrations consistently between 40 and 60 mEq/liter. Each has chronic Pseudomonas bronchitis, and all lack digestive symptoms. Laboratory findings indicate the preservation of exocrine pancreatic function. The patients include two of five children in one family and two of four in another. In a third family, one of five siblings has an intermediate sweat chloride concentration, but another has a typical fibrosis value (105 mEq/liter). One patient died of respiratory failure; results of an autopsy showed bronchiolectasis typical of cystic fibrosis, but minimal pancreatic changes. The data suggest a genetic basis for this variant of cystic fibrosis. These patients may be homozygous for a portion of a closely linked multigene cystic fibrosis locus or may have modifier genes that ameliorate the pancreatic and sweat lesions.(JAMA 239:2676-2680, 1978)

• Nasal polyposis complicated the course of cystic fibrosis in 157 (26%) of 605 patients. Onset before age 5 years or after age 20 years was rare. Polyposis was the initial symptom of cystic fibrosis in 13 patients. Common symptoms included obstruction to nasal air flow, mouth breathing, epistaxis, and rhinorrhea. Intranasal and oral corticosteroids and antihistamines were ineffective in preventing recurrences but did occasionally afford symptomatic relief of obstruction. Nineteen (31%) of 62 patients who never had surgery had spontaneous and permanent disappearance of polyps. Simple polypectomy was an adequate procedure for patients with substantial nasal symptoms. There were no visual complications. Other surgical complications were rare. Children and adolescents with nasal polyps should have sweat tests by pilocarpine iontophoresis to rule out cystic fibrosis.(Am J Dis Child 1982;136:1067-1070)

Extract: The retrograde perfusion assay of Mangos for the sodium reabsorption inhibitory effect in sweat and mixed saliva from patients with cystic fibrosis (CF) was modified by (1) using the second parotid gland of the rat as a control, (2) carefully controlling the quantity of saliva perfused into the rat parotid gland so that the ratio of milliliters perfused to gram dry gland weight fell between 1.8 and 2.8, and (3) reporting the inhibitory effect as percentage of inhibition of the rate of sodium reabsorption (RNa) in tne perfused gland calculated from the difference between the RNA'S in the two glands. Using this modified assay we were able to confirm that significant differences exist in the percentage of inhibition of RNacaused by CF and normal mixed saliva (47.0 ± 24.8 and 18.0 ± 8.3, mean ± SD). In addition, similar significant differences in the percentage of inhibition of RNaby submandibular gland secretions (39.7 ± 13.5 and 16.0 ± 11.8), sublingual gland secretions (39.5 ± 6.0 and 19.7 ± 14.3), and submucosal gland secretions (34.0 ± 11.7 and 21.7 ± 12.7) between CF and normal subjects were observed. However, parotid gland secretions from CF subjects showed no increased inhibitory effect (12.5 ± 7.9 and 12.5 ± 6.6). These findings demonstrate that the sodium reabsorption inhibitory effect is produced by the secretions from some but not all salivary glands of patients with CF.Speculation: These results indicate that the substance or substances responsible for the sodium reabsorption inhibitory effect of CF secretions is produced by cells present in submandibular, sublingual, and submucosal glands of patients with CF. Because mucus-producing cells are abundant in submandibular, sublingual, and submucosal glands, but are sparse in parotid glands (1) we suggest, as have Johansen et al. (4), that the inhibitory effect is in some way related to the mucous secretory product of the cystic fibrosis glands.

Pulmonary function and cardiopulmonary complications were studied in a group of 40 patients with cystic fibrosis who reached the age of 25 years. Mean values for vital capacity (VC), functional residual capacity, residual volume (RV), the ratio of RV over total lung capacity (RV/IXC), conductance, and the ratio of the forced expiratory volume in one second over VC were abnormal. There was a variable pattern of progression from patient to patient. The men differed from the women only in that they had a significantly larger TLC and inspiratory capacity than the women. The resultant preservation of VC may have an advantage for survival in those patients in whom it is observed. Pseudomonas aeruginosawas encountered with increasing frequency with age. Massive hemoptysis did not result in early death. The occurrence of right-sided heart failure secondary to cor pulmonale, with or without respiratory failure, was a poor prognostic sign.

Extract: Using the total body plethysmograph, a method for the measurement of lung volume and airway resistance was developed for infants and young children of 1 month-5 years of age. The subjects were studied in a supine position using a reproducible method of sedation. The procedure providing the most consistent results involved use of a Rendell-Baker mask directly controlled by the operator while the subjects were breathing through the nose. Availability of an oscilloscope permitted immediate detection of pressure leaks, artifacts, and abnormal patterns during each determination and minimized potential errors during the study of each subject. Care was required to avoid pressure on the tip of the nose because an abnormally high airway resistance resulted.The logarithmic relation of thoracic gas volume (TGV) at functional residual capacity (FRC) to body length for 52 normal subjects compared well with results obtained on newborn infants and with those obtained on older subjects. The equation was: TGV at FRC, litters = 1.57 × 10-5× length, cm2.238(correlation coefficient = 0.948). The logarithmic relation of airway conductance to TGV was: conductance, liters/sec/cm H2O = 0.1431 TGV, liters0.6441(correlation coefficient = 0.835). Comparison with older subjects was limited by the difference in airflow rates at which the airway conductance was determined (0.06-0.28 liters/sec versus about 0.5 liters/sec for adults) and by the use of sedation and nasal breathing in this study; adults are studied a wake and during mouth breathing. Comparison of our conductance values with those obtained on unsedated newborns suggests that either sedation alters the airway resistance or that some change occurs in the airway size-lung volume relation during the first weeks of life.Examples of the application of this method to patients with asthmatic bronchitis and cystic fibrosis of the pancreas are provided.Speculation: It is possible that an airflow-lung voliume-airway resistance relation exists throughout life; however, the results presented in this study, combined with those previously presented on newborns for airway resistance, suggest that a change may occur in the relation of the size of the airways to lung volume during early infancy, or that sedation alters airway resistance. Development of this and other methodology should permit more adequate studies of the early changes in pulmonary physiology associated with growth and the acute and chronic pulmonary conditions seen during the first 5 years of life.

The effect of corticotropin (adrenocorticotropic hormone [ACTH]) and cortisone on the acute state of the nephrotic syndrome has been described by a number of workers.* That endogenous corticotropin may be responsible for spontaneous remissions is suggested by diuresis following measles and other infections complicating the disease. Also, in one patient whom we observed during the occurrence of a spontaneous remission, we found an increase in urinary cortins and 17-ketosteroids, a fall in eosinophile count and an increase in uric acidcreatinine ratio immediately preceding the diuresis.4 It is the purpose of this communication to try to evaluate the ultimate value of these hormones when given in short-term courses by reviewing our observations in 64 infants and children who had the nephrotic syndrome and who were treated with either corticotropin or cortisone during the past four and one-half years.In accordance with a recently proposed classification,5 no effort will be

Explants of tracheal epithelium from each of six human neonates were exposed to both 80 and 20 oxygen under otherwise identical culture conditions. Cessation of ciliary movement and carbon particle transport occurred after 48–96 hr of exposure to 80 oxygen, but not after 168 hr of exposure to 20 oxygen.

Extract: The total body plethysmograph method of DuBois et al. [7] for measurement of lung volume and airway resistance was adapted to the study of newborn infants. A Rendell-Baker mask directly controlled by the operator proved by trial and error to minimize the chances of pressure leaks and undesirable pressure on the nose and allowed the mandible to be pulled forward to minimize pharyngeal obstruction. Use of an oscilloscope for direct visualization of flow and pressure tracings was essential in order to detect immediately pressure leaks, artifacts, and abnormal patterns during measurements of both lung volume and airway resistance.Interpretation of the measurements of airway resistance and of the relation of conductance to lung volume over a wide range of age and lung volumes requires that the flow rates at which measurements are made be recorded, along with lung volumes.In 51 newborn infants, an airway resistance value of 19.2±5.6 cm H2O/l/s was observed. Thoracic gas volume at functional residual capacity was 89.9±15.5 ml. The resulting mean value for conductance (reciprocal of airway resistance), 0.052 l/s/cm H2O, fell above the calculated regressions of conductance versus lung volume determined by Briscoe and DuBois [3], who used data obtained from older children and adults. Direct comparison is limited since airway resistance in the older subjects was usually obtained using panting flow rates of 0.5 l/s, while the infants in this study had flow rates of approximately 0.1 l/s at the time airway resistance was measured.Speculation: Confirmation of the presence of the major expiratory flow-limiting segment in the nasal airway of newborn and small infants is needed. This location suggests a physiologic means for slowing expiratory flow and thus maintaining expiratory intraluminal pressure in the tracheobronchial tree, which might protect the compliant trachea and major bronchi from compression by positive intrapleural pressure in obstructive pulmonary disease. It is possible that there is an airflow-lung volume-airway resistance relation throughout life; however, a wide range of control data will be required to establish such a relation.