Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients.

The effect of nocturnal oxygen therapy on mortality and morbidity rates and on progression of disease was tested in a double-blind, randomized trial of 28 subjects with advanced cystic fibrosis. Patients were selected on the basis that their awake arterial oxygen tension was less than 65 mm Hg when they were clinically stable. Oxygen was prescribed in 1 L/min increments to obtain an awake arterial oxygen tension of greater than or equal to 70 mm Hg. Subjects received humidified oxygen or room air from modified concentrators. They were enrolled over a 3-year period and followed for an average (+/- SD) of 26 +/- 9 months. The average number of hours per night of concentrator use was 5.3 +/- 3.2 hours in the air group and 7.0 +/- 1.9 hours in the oxygen group. Over the follow-up period there were four deaths in each group, and oxygen therapy had no significant effect on the frequency of hospitalizations. Progression of disease was ascertained from nutritional status, pulmonary function, blood gas values, exercise ability, and right ventricular ejection fraction response to exercise (as measured by equilibrium-gated radionuclide angiocardiography), and psychologic status was measured by standardized tests of mood, self-esteem, and cognitive function; group comparisons for the first year revealed no significant differences; however, school or work attendance was maintained in the oxygen group but deteriorated in the air group. Clinical signs of cor pulmonale were documented during follow-up in 10 patients in toto, and all lived at least 9 months from the onset of these signs. The lack of association between the onset of these signs and imminent death, or the usefulness of measurements of the maximal oxygen uptake during progressive exercise and the right ventricular ejection fraction response to exercise as prognostic indicators, suggest that death may not be the result of cor pulmonale. We conclude that nocturnal oxygen treatment in patients with cystic fibrosis did not appear to affect mortality rates, the frequency of hospitalizations, or the progression of disease; oxygen use should be instituted only after the development of symptoms related to hypoxemia.

Sources of error in flow-volume curves. Effect of expired volume measured at the mouth vs that measured in a body plethysmograph.

The popularity of the maximum expiratory flow-volume curve (FVC) is in part due to the effort independence of expiratory flow. Of interest are expiratory flow rates at specific lung volumes, usually 50 and 25 percent of vital capacity (VC); Vmax50 and Vmax25, which make accurate assessment of lung volumes essential. Changes in lung volume during the test are due to both the volume of gas expired and the volume change due to gas compression (Vcomp). In normal subjects, Vcomp is small but may be considerable in those with airflow obstruction. When the FVC is measured in a plethysmograph (FVCp), both expired volume and Vcomp are measured. When the volume of the FVC is derived from gas expired at the mouth (FVCm), Vcomp is not considered and differences in Vmax25 or Vmax50 may occur. The magnitude of these errors was assessed in 30 children and young adults: nine normal subjects, ten with cystic fibrosis (CF) and 11 with asthma. For Vmax50, use of FVCm instead of FVCp resulted in an error of 8 +/- 7 percent (mean +/- 1 SD) in the normal subjects compared to 32 +/- 23 in those with CF (p less than 0.01) and 24 +/- 18 for those with asthma (p less than 0.05). For Vmax25, the errors were similar. These errors were not predictable from FEV1 or RV/TLC but were related to a combination of expiratory effort, the shape of the FVCp, and the absolute volume of gas that was being compressed (p less than 0.0001). These findings suggest that expiratory flows in the FVCm are not effort-independent in the face of significant airflow obstruction and that comparisons of values derived from an FVCp with those from an FVCm may not be valid.

An alternate method for the determination of functional residual capacity in a plethysmograph.

The validity of measuring thoracic gas volume using a single inspiratory effort against an occlusion (Vtginsp) was determined in children and young adults (8 normal control subjects and 17 patients with cystic fibrosis [CF] or asthma). In addition, the validity of the measurement of Vtg at FRC in children at a low panting frequency (Vtgpant) was also determined. During both the panting (encouraged to be about 1 Hz) and inspiratory maneuvers, mouth pressure (Pm) and esophageal pressure (Pes) were measured simultaneously. Hence, Vtgpant and Vtginsp were determined using both delta Pm and delta Pes. Vtginsp using delta Pm was found to be similar to Vtginsp using delta Pes. Values for Vtgpant using either delta Pm or delta Pes were also found to be similar. The percent difference between Vtginsp (using delta Pm) and the average of Vtgpant and Vtginsp (using delta Pes for both) was calculated as an indication of the error of the inspiratory method. The error ranged from -13 to +13% and did not correlate with indices of air-flow limitation or hyperinflation. We have found that Vtginsp can be used to determine FRC in normal children and young adults as well as in those with CF or asthma. In addition, we have also validated the use of Vtgpant at a low panting frequency in these subjects.

Trapped gas and airflow limitation in children with cystic fibrosis and asthma.

Trapped gas (TG) has been shown to be present in cystic fibrosis (CF) and asthma, but its relationship with airflow limitation (AL) has not been explored. TG was defined as the difference between the functional residual capacity measured by body plethysmography [FRC(BP)] and that measured by helium dilution [FRC(He)] expressed as a percentage of total lung capacity (TLC). We studied 21 children with CF and 15 with asthma who had a similar degree of AL and hyperinflation, however the children with CF had greater amounts of TG compared with asthma [15% +/- 2 (mean +/- 1 SE) vs 8 +/- 2, P less than 0.05]. Mixing efficiency (ME), an index of the distribution of ventilation, was found to be lower in the CF children than in those with asthma (34 +/- 4 vs 54 +/- 4). In CF, TG correlated with forced expiratory flow between 25 and 75% of vital capacity (FEF25-75), ME, RV/TLC, and maximal expiratory flow rates at 25 and 50% of vital capacity (Vmax25 and 50, respectively; r = -0.66, -0.61, 0.72, -0.71, -0.74). ME also correlated with the above measures. In asthma, TG did not correlate with the FEF25-75, ME, RV/TLC, Vmax25, or Vmax50. Furthermore, TG was frequently found in patients with asthma with moderate AL while it was often absent in patients with severe AL. For both CF and asthma, neither the severity of AL nor the magnitude of the TG could be predicted from the increase in Vmax50 with helium (delta V50).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between the partial pressure of arterial oxygen and airflow limitation in children with cystic fibrosis.

To assess whether it would be possible to avoid repeated arterial blood sampling in children with cystic fibrosis, the relation between the forced expiratory flow at 25% to 75% of the vital capacity (FEF25%-75%) and the partial pressure of arterial oxygen (PaO2) was examined. The PaO2 and the logarithm of the FEF25%-75% (expressed as a percentage of that predicted) showed the strongest correlation (r = 0.89, p less than 0.001). Although this relation cannot be used when an accurate value for the PaO2 is required, it can sometimes be useful for determining the need for an arterial puncture.

Immediate and long-term effects of chest physiotherapy in patients with cystic fibrosis.

Both the immediate and long-term effects of chest physical therapy administered by a parent were evaluated in eight children with cystic fibrosis. Spirometric and plethysmographic evaluations were performed pre-CPT and at 5 and 30 minutes post-CPT. The pre-CPT measurements after a three-week period with no CPT were compared with the values while receiving CPT on a regular twice daily basis. There was a significant decrease after three weeks without CPT for FVC (P less than 0.025), FEV1 (P less than 0.005), FEF25-75 (P less than 0.005), and Vmax60TLC (P less than 0.025). When the patients had been receiving CPT on a regular basis, the only immediate effect was an increase in PEFR after 30 minutes post-CPT (P less than 0.05). After three weeks without CPT, there were increases at 30 minutes post-CPI for FVC (P less than 0.005) and Vmax60TLC (P less than 0.05). These findings indicate that although there may be little immediate functional improvement when CPT is received on a regular basis, a three-week period without CPT leads to a worsening of the functional status, which is reversed with renewal of regular CPT.

Histamine inhalation challenge in children: a comparison of two methods.

Airway reactivity in children is often assessed using a histamine inhalation challenge test. The bronchoconstrictor agents are usually delivered by five slow inspiratory capacity (IC) maneuvers, the IC method. We compared the IC method with a tidal breathing (TB) method in 30 children; 11 were normal, six were under investigation for asthma and 13 were known asthmatics. None of the normal children responded to either method, whereas 18 out of the 19 (95%) known or suspected asthmatics responded to the TB method while only 13 out of 19 (68%) showed a significant reduction in FEV1 when the IC method was used. The concentration of histamine necessary to cause a 20% reduction in FEV1 was less for the TB method, suggesting that in children the TB method will produce airway reactivity more quickly than the IC method.

The effect of digoxin on exercise capacity and exercising cardiac function in cystic fibrosis.

The ability of digoxin to increase exercise capacity and stroke volume (SV) during exercise was evaluated in ten patients with cystic fibrosis (CF) ages 12 to 20 years with moderate to severe degrees of airway obstruction but no history of heart failure. A double-blind crossover trial of digoxin versus placebo was carried out. An evaluation of exercise performance was undertaken upon entry into the study, and after each of the one-week periods in which digoxin 0.25 mg/day or placebo was taken. Exercise testing consisted of a progressive exercise test on a cycle ergometer to measure maximum work capacity (Wmax) and a steady state test at 2/3 of the baseline Wmax. During the steady state test, the oxygen consumption and carbon dioxide production were measured and cardiac output (Q) was calculated by the indirect Fick (CO2) method. From Q and heart rate (HR), SV was derived. After digoxin, Wmax was unchanged. On steady state exercise HR was unchanged, but there was a slight but significant fall in Q due to a fall in SV. The decrease in SV was associated with exercising hypoxemia. We conclude that digoxin did not increase exercise capacity or improve exercising cardiac function in patients with moderate to severe airway obstruction due to CF.

Primary lung abscess in childhood: the long-term outcome of conservative management.

Fourteen cases of primary lung abscess in childhood were treated with antibiotics alone. The only organism discovered was Staphylococcus aureus. All the children recovered. Roentgenographic abnormalities took from six weeks to more than five years to resolve. Recently, follow-up of 11 of the 14 children was performed an average of nine years after treatment of the abscess. In all children, the clinical status, lung volumes, and expiratory flow rates were normal, except in two with asthma. A conservative approach to the management of primary lung abscess in children is recommended.

alpha-Fetoprotein and cystic fibrosis.

Because of unconfirmed reports that the serum level of alpha-fetoprotein (AFP) is high in children with cystic fibrosis and intermediate in their siblings and parents, this level was measured in 25 children with cystic fibrosis, 26 of their siblings, 42 of their parents and 31 age-matched children without cystic fibrosis who were attending outpatient clinics of the Montreal Children's Hospital. Liver function tests were performed at the same time since patients with liver disease may have unusually high serum AFP levels and patients with cystic fibrosis often have liver involvement. AFP was not detected in any of the serum samples, and the results of the liver function tests were normal in all but 1 individual, a control subject. In simultaneous assays of serum from children with ataxia telangiectasia, however, high AFP levels were detected in 15 of 16 samples. Thus, measurement of the serum AFP level is of no value in detecting carriers of the cystic fibrosis gene.

Ventilation, respiratory center output, and contribution of the rib cage and abdominal components to ventilation during CO2 rebreathing in children with cystic fibrosis.

Although there has been extensive research into the control of breathing in adults with chronic obstructive lung diseases, there is little information in this area in children with cystic fibrosis (CF). The purpose of this study was to investigate the respiratory response of children with CF to CO2 under hyperoxic conditions. Using a standard CO2 rebreathing technique, we studied 14 children with CF. We evaluated their response to CO2 in terms of ventilation (VE), mean inspiratory flow rate (VT/TI), and the pressure generated at the mouth after 0.1 s of an inspiratory effort against an occlusion (P0.1). In order to understand the contributions of the rib cage and abdominal components to ventilation, we assessed the volume change in each compartment by attaching magnetometers to the chest and abdomen. Overall changes in lung volume were assessed in a volume displacement plethysmograph. We found that, when corrected for the height of the child, the slope of VE versus end tidal CO2 (PETCO2), as well as the slope of VT/TI versus PETCO2 correlated significantly with the degree of airway obstruction as expressed by the forced expiratory flow between 25 and 75% of vital capacity. The values for P0.1 were all within the normal range and showed no correlation with the degree of airway obstruction. The contribution of the rib cage and abdomen to ventilation during rebreathing was similar to that previously reported for adults. No changes were observed in functional residual capacity during rebreathing. We showed that tests involving a mechanical response to CO2 correlated with the degree of airway obstruction, but there was no evidence that the neuromuscular drive was abnormal.

Is anti-Pseudomonas therapy warranted in acute respiratory exacerbations in children with cystic fibrosis?

A controlled study was designed to clarify the indications for antibiotic therapy in children with advanced cystic fibrosis hospitalized with respiratory exacerbations. Twenty-two children with severe CF and signs of acute lower respiratory infection were randomly assigned to receive either cloxacillin or carbenicillin plus gentamicin administered intravenously for ten days. Other aspects of therapy were constant. The groups were comparable in all respects and Pseudomonas aeruginosa was the predominant sputum pathogen in most patients. Clinical improvement, chest radiograph changes, evidence of airway obstruction, and bacteriologic flora of sputum were no different regardless of the regimen used. These results suggest that the use of anti-Pseudomonas medication in these children may not always be necessary. These observations need to be confirmed by blind-controlled studies in larger numbers of patients with mild as well as severe respiratory involvement.

Upper airway obstruction in children. The value of inspiratory-expiratory flow-volume curves.

The physiological assessment of upper respiratory tract obstruction using inspiratory-expiratory flow-volume curves is a valuable non-invasive procedure in children. The technique employed at the Montreal Children's Hospital with appropriate case material is presented. Although flow-volume curves can reliably diagnose and localize a large airway obstruction, these lesions are readily monitored by spirometric testing.

Prone immersion physical exercise therapy in three children with cystic fibrosis: a pilot study.

Prone immersion physical exercise therapy has been used successfully in the physical rehabilitation of middle-aged adults with moderate to severe chronic obstructive pulmonary disease. The purpose of this pilot project was to evaluate the effects of PIPE therapy in children with cystic fibrosis. Three children with CF, two boys aged 6 and 14 years and one girl aged 15 years, voluntarily participated in the experimental training program. The patients performed individualized group exercise three times a week on alternate days for 28 consecutive weeks at an intensity of approximately 75 percent aerobic capacity. Duration of exercise gradually increased from 15 (3 x 5 minutes) to 60 (3 x 20 minutes) minutes while the rest period after each exercise was constant at two minutes. PIPE training resulted in increased physical work capacity and maximal oxygen consumption in all three subjects. Curiously, these changes were not accompanied by training bradycardia.

Assessment of ventilation-perfusion inequality by aADN2 in newborn infants.

The contribution (Qo/Qt) of gas-filled air spaces with reduced ventilation-perfusion ratio (VA/Qc) to the production of total venous admixture in nondistressed premature infant and newborn infants with transient tachypnea was assessed by the aADN2 and AaDo2. The mean value for Qo/Qt in both nondistressed prematures and infants with transient tachypnea was 0.08. In both groups this represented about 30% of total venous admixutre.

Late effect of nocturnal mist tent therapy related to the severity of airway obstruction in children with cystic fibrosis.

To evaluate the long-term effect of nocturnal mist tent therapy on the progression of airway obstruction in children with cystic fibrosis (CF) of varying severity, two matched groups each consisting of 24 children with CF were studied during 18 months on mist tent therapy and 18 months of therapy. The progression in airway obstruction was measured by change in serial measurements of maximal midexpiratory flow (MMEF), from which a regression equation of MMEF against time was obtained for each individual. Changes in MMEF value with or without therapy were compared in patients matched for severity of disease as indicated by initial MMEF values. For the group as a whole no differences were found in the progression of the airway obstruction whether the patients received mist tent therapy or not. This therapy failed to benefit any of the groups of children with CF who had early, moderate, or advanced airway obstruction as judged from their initial MMEF value. It is concluded that nocturnal mist tent therapy neither decreases airway obstruction nor prevents its progression in children with CF.