Relationship of arterial-alveolar nitrogen tension to alveolar-arterial oxygen tension, lung volume, flow measurements, and diffusing capacity in cystic fibrosis.

Pulmonary function in children with cystic fibrosis was assessed by the arterial-alveolar PN2 difference adjusted to sublingual temperature. The resulting values were compared with the alveolar-arterial PO2 difference, arterial PCO2, and standard measurements of lung volume, flow, and diffusing capacity. The arterial-alveolar PN2 difference was nearly one half of the PO2 difference, both early in the disease and at a more advanced stage. Analysis taking into account the O2 dissociation curve and the possibility that alveolar temperature is higher than sublingual temperature suggested that all of the PO2 difference could be explained in terms of ventilation-perfusion imbalance in gas-filled units of the lung. Reduction of fractional CO uptake with increasing PN2 difference suggested that the decrease in diffusing capacity in cystic fibrosis may be explained by ventilation-perfusion inequality. A significant relationship between arterial PCO2 and the PN2 difference supported the view that ventilation-perfusion inequality is the cause of CO2 retention when present. The PN2 and PO2 differences were abnormal before the standard tests of lung volume and flow, but in general, the correlation was excellent. Because the PN2 difference was not superior to the PO2 difference in detecting early disease, and because the technical problems in its measurement are considerable, it is not recommended as a routine measurement.     

The repeatability of forced expiratory volume measurements in adults with cystic fibrosis

STUDY OBJECTIVE: To determine the repeatability of measurements of FEV(1) in adults with lung disease due to cystic fibrosis (CF). DESIGN: Single cohort study nested within a randomized controlled trial. SETTING: Adult CF of a university teaching hospital. Subjects were participants in a randomized trial of an experimental mucolytic drug. PATIENTS: Twenty-one adults (mean age, 27.5 +/- 9.2 years [+/- SD]) with CF and mild-to-moderate airflow obstruction (FEV(1) 70 +/- 15% predicted). Patients were in clinically stable condition prior to and during the study. INTERVENTIONS: Repeated FEV(1) measurements were obtained at specific times of the day for 9 consecutive days, for a total of 31 measurements from each subject. Statistical measures of repeatability were calculated. Variation over the course of 1 day and variation from 1 day to the next were examined separately. Measurements and results: For day-to-day FEV(1) measurements, the within-subject SD was 0.145 L (4.5% of predicted), indicating greater variation compared to values previously established in normal subjects. The coefficient of repeatability indicated that day-to-day measurements could differ by as much as 13% of predicted in the absence of clinical change. For measurements within a single day, variation was not observed to be greater than normal. CONCLUSIONS: In adults with CF, day-to-day variation in FEV(1) measurements is greater than normal and similar to that seen in other obstructive lung diseases. Changes in FEV(1) over time in adults with CF can likely be interpreted using the same criteria that apply to asthma or COPD.     

Tidal expiratory flow limitation and chronic dyspnoea in patients with cystic fibrosis.

Cystic fibrosis (CF) eventually leads to hyperinflation linked to tidal expiratory flow limitation (FL) and ventilatory failure. Presence of FL was assessed at rest in 22 seated children and adults with CF (forced expiratory volume in one second (FEV1) range: 16-92% predicted), using both the negative expiratory pressure (NEP) technique and the "conventional" method based on comparison of tidal and maximal expiratory flow/volume curves. In addition, chronic dyspnoea was scored with the modified Medical Research Council (MRC) scale. Measurements were made before and 15 min after inhalation of salbutamol. With NEP, FL was present in only three malnourished patients, who had the lowest FEV1 values (16-27% pred) and claimed very severe dyspnoea (MRC score 5). By contrast, an additional seven patients were classified as FL with the conventional method. Six of these patients had little or no dyspnoea (MRC scores 0-1). Salbutamol administration had no effect on the extent of FL, and the concomitant decrease in functional residual capacity (FRC) was too small to play any clinically significant role. This study concluded that in seated patients with cystic fibrosis, expiratory flow limitation is absent at rest, unless the forced expiratory volume in one second is <30% predicted. If present, expiratory flow limitation is associated with severe chronic dyspnoea. The conventional method for assessing expiratory flow limitation is not reliable and bronchodilator administration has little effect on expiratory flow limitation.     

Does expiratory flow limitation predict chronic dyspnoea in adults with cystic fibrosis?

Tidal expiratory flow limitation (EFL) may promote dynamic hyperinflation and contribute to chronic dyspnoea. The purpose of this study was to assess the contribution of EFL to chronic dyspnoea in adults with cystic fibrosis (CF). The presence of EFL was determined in 102 adults with stable CF (forced expiratory volume in one second (FEV1) 17.3-91.5% predicted) and 20 age-matched control subjects using the negative expiratory pressure technique. Measurements of inspiratory capacity (IC) and spirometry were performed, and chronic dyspnoea was evaluated using the modified Medical Research Council scale. EFL was present in 34 subjects (33%), with 18 subjects flow limited in the sitting position and 16 subjects flow limited only in the supine position. Flow limitation in the sitting position was associated with older age and lower FEV1 compared with flow-limited supine position and non-flow-limited subjects. A significant reduction in IC accompanied EFL in both the sitting and supine positions. Flow limitation in the sitting position was associated with significantly higher levels of chronic dyspnoea. Ordinal regression analysis indicated that EFL was the best predictor of chronic dyspnoea in a model that included FEV1 % pred. Expiratory flow limitation in cystic fibrosis is associated with reduced forced expiratory volume in one second, older age and dynamic hyperinflation. Expiratory flow limitation significantly contributes to chronic dyspnoea in cystic fibrosis.     

Home measurement of oxygen saturation during sleep in patients with cystic fibrosis

Feasibility and reproducibility of home measurement of arterial oxygen saturation (SaO2) were evaluated in 14 clinically stable patients with cystic fibrosis (CF). Changes in SaO2 during sleep were compared to the clinical status and pulmonary function while awake to identify predictors of nocturnal oxyhemoglobin desaturation. Each patient was assessed by clinical score, spirometry, and arterial blood gas analysis within 72 hours of the overnight study. Eight patients were studied on more than one occasion to assess dependence of SaO2 on position and reproducibility of overnight studies. A pulse oximeter stored up to 8 hours of nocturnal SaO2 measurements in its memory. Off-line analysis of trend data provided the proportion of sleep with SaO2 less than 90% and less than 85%. We found that patients with daytime PaO2 less than 60 mm Hg spent greater than 80% of their sleep with SaO2 less than 90%, while those with PaO2 greater than 70 mm Hg spent less than 20% of the night with SaO2 less than 90%. Patients with daytime PaO2 of 67-70 mm Hg were desaturated to less than 90%, from 0 to 98% of the night. No consistent body position dependence of daytime SaO2 was found. Home measurement of SaO2 during sleep was reproducible, with a difference on two repeat occasions of 4% +/- 2 (mean +/- SEM) for %time with SaO2 less than 90% and 3% +/- 2 for %time with SaO2 less than 85%. The severity of hemoglobin desaturation during sleep could not be reliably predicted from clinical scores or awake pulmonary function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predicting survival in end-stage cystic fibrosis

The natural history of cystic fibrosis (CF) is unpredictable and the optimal timing for lung transplantation in end-stage disease uncertain. Predicting survival based on FEV₁ alone remains controversial and therefore the aim of this study was to assess the value of walk test performance in pre-transplant assessment.Retrospective review of adult patients with end-stage CF who underwent transplant assessment between 1988 and 2004 including a documented walk test on room air, but who died before transplant. The six-minute walk test (6MWT) was used between 1988 and 1993 and the shuttle walk test (SWT) thereafter, the two cohorts were therefore individually assessed.A total of 121 patients were identified. The median (IQR) survival in patients performing SWT (n = 77) and 6MWT (n = 44) was 363 days (226, 566) and 433 days (232, 844), respectively, with survival in both cohorts significantly associated with pre-test (resting) heart rate (HR) (p < 0.03), but not distance walked, pre-test SpO₂, FEV₁ or BMI. It was predicted that 85% of patients performing SWT with a resting HR of 120 bpm, 70% of those with a HR of 109 bpm (cohort median) but only 25% with a HR of 72 bpm would die within 500 days. Distance walked in the SWT was significantly related to pre-test HR (p < 0.01), SpO₂ (p < 0.01) and Borg score (p = 0.016) when performing linear regression. Only pre-test HR remained significant when performing multiple regression.Resting heart rate was the only consistent parameter in this study at predicting a high risk of dying on the transplant waiting list.     

Density dependence of the maximal expiratory flow volume curves in normal and asthmatic children.

We have studied the maximal expiratory flow volume curves with air and with an 80% helium-oxygen mixture, using 12 normal and 33 asthmatic children chosen according to clinical, functional and immunological criteria. In the normal children, the average delta Vmax (difference between the maximal flow in HeO2 and in air at corresponding lung volumes) was 49% and was similar from 60% to 20% of vital capacity. The iso flow volume (lung volume level at which the HeO2 and air flow volume curves intersect) was 3% of vital capacity. Eleven of the asthmatics were non-responders to the helium mixture (no significant differences in flow between HeO2 and air curves), five at 50% and 25% VC and six at only 25% VC. The other 22 asthmatics were responders, but nine of them showed a rise of the iso flow volume. Eight subjects showed no obstruction according to the flow volume curves in air; three of these had an abnormal response to the helium mixture. All the non-responders at 50% VC and half of the non-responders at 25% VC had a clinical history of recurrent infections. These results suggest, firstly, that when there is no history of recurrent infections, the site of obstruction in asthmatic children is mainly central. This does not exclude a coexisting peripheral obstruction which could persist after recovery of the central component. Secondly, by studying the HeO2 response at 25% VC, we can get more information than by measuring only the delta Vmax50 or iso flow volumes.     

Effect of body position on maximal expiratory pressure and flow in adults with cystic fibrosis

Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) are used as surrogate measures of cough and huff strength. Some body positions (particularly head-down tilt) significantly affect these measures in people with normal respiratory function and with chronic obstructive pulmonary disease. This may have implications for people with cystic fibrosis (CF), who use coughing and huffing and may use gravity-assisted drainage positions for airway clearance. Previous research concluded that body position does not affect MEP in people with CF, although head-down tilt was not examined and PEFR was not measured. This study investigated the effect of body position on MEP and PEFR in 20 adults with stable CF. Repeated measures of MEP and PEFR were performed across seven positions (standing, chair-sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees , supine, side-lying, and side-lying with head-down tilt 20 degrees ) in random order. During testing, reflux sensation and oxygenation were monitored. MEP was significantly reduced in side-lying and in the head-down tilt position. PEFRs were significantly reduced in the three-quarters sitting, supine, side-lying, and head-down positions. Oxygenation and reflux scores were worst in the head-down position. Despite statistical significance, the differences observed between positions in this stable population were of small magnitude. The effect of body position on MEP and PEFR may be more relevant during airway clearance treatments of the acutely unwell person with CF.     

The “worth” of routine spirometry in a cystic fibrosis clinic

In our cystic fibrosis clinic, all patients older than 6 years perform spirometry at each visit just before being seen by the health care team. Upon review, we determined that our perceived rationale for this practice was that the medical history fails to detect deterioration in a sizable minority of patients whose pulmonary decline can be detected by spirometry. Furthermore, the literature and our own experience indicates that physical examination frequently will not detect changes in pulmonary status until the changes are advanced. As part of an ongoing quality/cost assessment, we decided to challenge our rationale for performing routine spirometry. Using standard methodology, we developed a six-item Likert style questionnaire, the purpose of which was to assess perceived changes in pulmonary symptoms since the last clinic visit. The questionnaire had an acceptable degree of internal consistency (Cronbach's alpha = 0.92), although the question about sputum production showed the least correlation with responses to other items. We administered the questionnaire to 103 consecutive different patients and examined the association between reported changes in symptoms and actual changes in spirometric outcomes. Overall, there was a statistically significant, but clinically weak association between symptom scores and change in FEV₁, r² = 0.16, P < 0.001. Twenty-three patients had a decline in FEV₁ of ⩾10% from one clinic visit to the next. Depending on the method used to place symptom scores into categories indicating that pulmonary symptoms were “worse,” “same,” or “better” than at the last clinic visit, 40–60% of these 23 patients indicated they felt the “same” or “better.” We conclude that spirometry is a justifiable part of all clinic visits for patients with cystic fibrosis, assuming that one would want to detect and treat declines in pulmonary status before they become advanced. Pediatr Pulmonol. 1998; 25:231–237. © 1998 Wiley-Liss, Inc.     

Thoracoabdominal asynchrony and ratio of time to peak tidal expiratory flow over total expiratory time in adolescents with cystic fibrosis.

Thoracoabdominal asynchrony (TAA) and the ratio of time to peak tidal expiratory flow over total expiratory time (TME/TE) have been used to assess airway obstruction in infants and adults. We obtained these measurements using calibrated respiratory inductance plethysmography (RIP) on 15 adolescents and young adults with cystic fibrosis (CF) and varying disease severity. The measurements were then compared to 15 normal age-matched controls. TAA was expressed as a phase angle (phi) calculated from the abdominal (AB) and ribcage (RC) signals acquired from scalar strip chart recordings. Using CODAS (DATAQ Instruments, Akron, OH) software, the analog signals were digitized, and the differentiated sum (AB + RC) signal was used to calculate TME/TE. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were obtained using RIP in all subjects. Subjects with CF had a significantly higher mean phi than the control subjects (15 degrees vs. 8 degrees, respectively, P = 0.01). In the CF patients the specificity of a high phi as an indicator of abnormality was 80%, while the sensitivity was 65%. There was no correlation in the magnitude of phi and disease severity as assessed by FVC or FEV1. There was no significant difference in TME/TE between the groups. We conclude that RIP-acquired phi, but not TME/TE, is a simple and useful method to detect the presence of airway obstructive disease. We speculate that the sensitivity of this method will increase in younger patients with more compliant chest walls and less air trapping. Longitudinal studies of phi in infants and young children with lung disease could help in assessing disease severity and progression in this population, in whom repeated measures are few and complex.     

The influence of fresh gas flow and inspiratory/expiratory ratio on tidal volume and arterial CO2 tension in mechanically ventilated surgical patients

The relative importance of fresh gas flow and inspiretory/expiratory ratio in determining delivered tidal volume and PaCO₂ was studied in anesthetized adult patients ventilated with a fixed ventilator bellows volume. The fresh gas flows studied were 2, 6, and 10 L/min, and inspiratory/expiratory ratio was either 1:2 or 1:4.5. Bellows volume and respiratory rate were held constant throughout the study. At the lowest fresh gas flow and smallest inspiratory/expiratory ratio, PaCO₂ was 43 ± 2 mm Hg. The PaCO₂ decreased progressively and significantly with each increase in fresh gas flow during ventilation with either inspiratory/expiratory ratio setting. PaCO₂ averaged 30 ± 3 during ventilation with the highest fresh gas flow and largest inspiratory/expiratory ratio. As fresh gas flow increased, PaCO₂ and tidal volume changed to a significantly greater degree in response to changes in inspiratory/expiratory ratio. These data demonstrate that altering either fresh gas flow or inspiratory/expiratory ratio can produce clinically significant perturbations in PaCO₂ and tidal volume during anesthesia. These perturbations occur even if bellows volume is held constant. Furthermore, changes in inspiratory/expiratory ratio will affect these parameters to a greater degree as fresh gas flow is increased.     

Nontuberculous mycobacterial infection in young children with cystic fibrosis

Although nontuberculous mycobacteria (NTM) are recognized pathogens in adolescent and adult patients with cystic fibrosis (CF), the role of NTM in younger CF patients is not well-defined. To explore NTM infection in CF patients less than 12 years old, a retrospective review was performed. Prevalence was estimated from routine mycobacterial cultures of bronchoalveolar lavage (BAL) specimens collected over a 3-year period. NTM-positive cultures were obtained from 9 of 258 BALs collected from 7 of 114 different patients (5 months to 11 years of age). Further data were acquired from microbiological and clinical records of all pediatric patients with CF over a 10-year period. A total of 17 patients had at least one positive mycobacterial culture at less than 12 years of age, 5 of whom had positive cultures before age 5. The most commonly identified organisms were Mycobacterium avium-complex and Mycobacterium abscessus. Of the 17 patients, 10 met American Thoracic Society (ATS) microbiological criteria for mycobacterial disease, and 7 did not. The two groups did not differ with respect to age, gender, or presence of other respiratory pathogens. Patients who met ATS microbiological criteria for disease were more likely to have positive smears for acid-fast bacilli and grow Mycobacterium abscessus from culture. These patients also had a greater decline in lung function over time than patients who did not meet the microbiologic criteria. These data suggest that NTM represent a clinically significant pathogen, even in young patients with cystic fibrosis.     

Effect of airway inflation pressure on forced expiratory maneuvers from raised lung volume in infants.

The raised lung volume technique is increasingly used to measure forced expiratory maneuvers in infants. However, there is no consensus regarding the optimal airway inflation pressure (P(inf)) required for such maneuvers, or the influence of small changes in P(inf) within and between infants. The aim of this study was to assess the effect of small differences (0.2-0.3 kPa) in P(inf) on forced vital capacity (FVC), forced expired volume in 0.5 sec (FEV(0.5)), and forced expired flow at 75% of vital capacity (FEF(75)), all derived from the raised volume rapid thoraco-abdominal compression (RVRTC) technique. Randomized paired forced expiratory maneuvers were obtained in 32 healthy infants ( 3.9-39.3 weeks old, 3.8-9.9 kg) with the safety pressure relief valve for P(inf) set to 2.7 kPa or 3.0 kPa (27 or 30 cm H(2)0). When mean (SD) P(inf) was increased by 8.4 (2.8)%, there was a significant (P < 0.01) increase in mean (SD) FVC, FEV(0.5), and FEF(75) by 5.8 (5.7)%, 6.1 (6)%, and 8.3 (16.2)%, respectively. In conclusion, relatively small differences in P(inf) will result in significant differences in FVC, FEV(0.5), and FEF(75) by RVRTC technique. Precision in setting and reporting the applied P(inf) is therefore essential, particularly if data are to be compared between centers.     

Peak expiratory flow measured with the Mini Wright Peak Flow Meter in children

We established pediatric reference values for peak expiratory flow rate (PEFR), using the Mini Wright Peak Flow Meter. The study was based on 1,566 Mediterranean white children, aged 7 to 14 years from Valencia (Spain) schools. Height was the biometric variable with the greatest correlation to PEFR in both sexes; significant differences were noted between males and females. Prediction equations and percentile tables are presented for each sex. The performance of the Mini Wright Peak Flow Meter was compared with that of a spirometer.