Abstracts: Cystic Fibrosis in Lungs

- Updated on August 3, 2021

Crit Care Med. 2003 Nov;31(11):2634-40.
Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation.
Laffey JG, Engelberts D, Duggan M, Veldhuizen R, Lewis JF, Kavanagh BP.
Lung Biology Program, The Research Institute and Department of Critical Care Medicine and Anesthesia, Hospital for Sick Children, Interdepartmental Division of Critical Care, University of Toronto, Ontario, Canada.
OBJECTIVE: Deliberate elevation of PaCO2 (therapeutic hypercapnia) protects against lung injury induced by lung reperfusion and severe lung stretch. Conversely, hypocapnic alkalosis causes lung injury and worsens lung reperfusion injury. Alterations in lung surfactant may contribute to ventilator-associated lung injury. The potential for CO2 to contribute to the pathogenesis of ventilator-associated lung injury at clinically relevant tidal volumes is unknown. We hypothesized that: 1) hypocapnia would worsen ventilator-associated lung injury, 2) therapeutic hypercapnia would attenuate ventilator-associated lung injury; and 3) the mechanisms of impaired compliance would be via alteration of surfactant biochemistry. DESIGN: Randomized, prospective animal study. SETTING: Research laboratory of university-affiliated hospital. SUBJECTS: Anesthetized, male New Zealand Rabbits. INTERVENTIONS: All animals received the same ventilation strategy (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O; rate, 42 breaths/min) and were randomized to receive FiCO2 of 0.00, 0.05, or 0.12 to produce hypocapnia, normocapnia, and hypercapnia, respectively. MEASUREMENTS AND MAIN RESULTS: Alveolar-arterial oxygen gradient was significantly lower with therapeutic hypercapnia, and peak airway pressure was significantly higher with hypocapnic alkalosis. However, neither static lung compliance nor surfactant chemistry (total surfactant, aggregates, or composition) differed among the groups. CONCLUSIONS: At clinically relevant tidal volume, CO2 modulates key physiologic indices of lung injury, including alveolar-arterial oxygen gradient and airway pressure, indicating a potential role in the pathogenesis of ventilator-associated lung injury. These effects are surfactant independent.

Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):399-405.
Injurious effects of hypocapnic alkalosis in the isolated lung.
Laffey JG, Engelberts D, Kavanagh BP.
Department of Critical Care Medicine and The Lung Biology Program, The Research Institute, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
Mechanical ventilation can worsen morbidity and mortality by causing ventilator-associated lung injury, especially where adverse ventilatory strategies are employed. Adverse strategies commonly involve hyperventilation, which frequently results in hypocapnia. Although hypocapnia is associated with significant lung alterations (e.g., bronchospasm, airway edema), the effects on alveolar-capillary permeability are unknown. We investigated whether hypocapnia could cause lung injury independent of altering ventilatory strategy. We hypothesized that hypocapnia would cause lung injury during prolonged ventilation, and would worsen injury following ischemia-reperfusion. We utilized the isolated buffer-perfused rabbit lung model. Pilot studies assessed a range of levels of hypocapnic alkalosis. Experimental preparations were randomized to control groups (FI(CO(2)) = 0.06) or groups with hypocapnia (FI(CO(2)) = 0.01). Following prolonged ventilation, pulmonary artery pressure, airway pressure, and lung weight were unchanged in the control group but were elevated in the group with hypocapnia; elevation in microvascular permeability was greater in the hypocapnia versus control groups. Injury following ischemia-reperfusion was significantly worse in the hypocapnia versus control groups. In a preliminary series, degree of lung injury was proportional to the degree of hypocapnic alkalosis. We conclude that in the current model (1) hypocapnic alkalosis is directly injurious to the lung and (2) hypocapnic alkalosis potentiates ischemia-reperfusion-induced acute lung injury.

Am J Clin Nutr 1999;69:913–9.
Energy expenditure and substrate utilization in adults with cystic fibrosis and diabetes mellitus
Ward SA, Tomezsko JL, Holsclaw DS, Paolone AM
Pediatric Pulmonary and Cystic Fibrosis Centers, Hahnemann
University Hospital, Philadelphia; the Department of Physical Education, Temple University, Philadelphia; and the Department of Physical Education and Exercise Science, Norfolk State University, Norfolk, VA.
Background: The onset of cystic fibrosis–related diabetes mellitus (CFDM) is often associated with a decline in clinical and nutritional status.
Objective: The purpose of this study was to characterize energy expenditure (EE) and substrate utilization during rest, exercise, and recovery from exercise in patients with CF diagnosed with diabetes mellitus.
Design: EE, substrate utilization, minute ventilation, tidal volume, and respiratory rate were calculated by indirect calorimetry during rest; a 30-min, low-to-medium-intensity exercise bout on a treadmill; and a 45-min postexercise recovery period (in reclining position) in 10 CF, 7 CFDM, and 10 control subjects between 18 and 45 y of age.
Results: In all 3 periods, minute ventilation was higher in the CF and CFDM groups than in the control subjects (P < 0.01). During rest and exercise, the CF and CFDM groups maintained EE values at the high end of the normal range of the control subjects. However, during recovery, EE was higher in the CF and CFDM groups than in the control group (P < 0.01).
Conclusions: EE may be higher than usual for the patients with CF and CFDM during periods of recovery from mild exercise or activity because of increased work of breathing consistent with higher ventilatory requirements. This information may be useful for patients receiving nutritional counseling who may choose to exercise regularly, but are concerned about possible weight loss.

Respiratory Physiology & Neurobiology 153 (2006) 217–225
Mechanical limitation during CO2 rebreathing in young patients with cystic fibrosis
Brigitte Fauroux, Fr´ed´eric Nicot, Pierre-Yves Boelle, Mich`ele Boul´e, Annick Cl´ement, Fr´ed´eric Lofaso, Monique Bonora
Armand Trousseau Hospital, Assistance Publique-Hˆopitaux de Paris, Paris, France
The aim of the study was to determine whether a decrease in the ventilatory response to carbon dioxide (CO2) in children with cystic fibrosis (CF) is related to a mechanical limitation of the respiratory muscle capacity. The ventilatory response during CO2 rebreathing was performed in 15 patients (mean forced expiratory volume in 1 s (FEV1): 37±21% predicted, mean arterial CO2: 41±5 mmHg). The slope of the minute ventilation normalised for weight per mmHgCO2 increment correlated negatively with respiratory muscle output, assessed by the oesophageal (p = 0.002), the diaphragmatic pressure time product (p = 0.01), and the tension time index (p = 0.005). In addition, this slope was correlated with dynamic lung compliance (p < 0.0001) and FEV1 (p = 0.03) but not with airway resistance and maximal transdiaphragmatic pressure. Therefore, an excessive load imposed on the respiratory muscles explains the blunting of the ventilatory response to CO2 in young patients with CF.

Respiratory Physiology & Neurobiology 152 (2006) 176–185
Respiratory factors do not limit maximal symptom-limited exercise in patients with mild cystic fibrosis lung disease
Jonathan D. Dodd, Sinead C. Barry, Charles G. Gallagher
Department of Respiratory Medicine and National Referral Centre for Adult Cystic Fibrosis, St. Vincent’s University Hospital, Dublin 4, Ireland
To evaluate whether respiratory factors limit exercise capacity in patients with mild cystic fibrosis (CF) lung disease (mean FEV1 =76±7.7% predicted) we stressed the respiratory system of seven patients using added dead space (VD). Primary outcomes were exercise duration (Exdur) and maximal oxygen uptake (VO2 max). Dyspnoea/leg-discomfort were assessed at end-exercise. Exdur was identical between control and VD studies (520±152 versus 511±166 s, p = NS) as was ¨VO2 max (1.6±0.5 versus 1.6±0.6 L/min, p = NS). Significant resting, sub-maximal and maximal workload increases in minute ventilation (VE) were detected (70.8±13.7 versus 79.5±16.9 L/min, p < 0.05). Analysis of breathing pattern revealed increases in VE were attributable to increases in tidal volume (2.0±0.5 versus 2.2±0.6 L, p < 0.05) with no change in respiratory frequency. There was no difference in dyspnoea/leg discomfort between tests. The increase in VE in response to VD, with no change in Exdur/VO2 max suggests maximal symptom-limited exercise limitation is not primarily limited by respiratory factors in mild CF lung disease. Focused investigation and treatment of non-respiratory factors contributing to exercise limitation may improve exercise rehabilitation in this patient group.

Chest. 1990 Jun;97(6):1317-21.
Importance of respiratory rate as an indicator of respiratory dysfunction in patients with cystic fibrosis.
Browning IB, D’Alonzo GE, Tobin MJ.
Department of Medicine, University of Texas Health Science Center, Houston.
Bedside measurement of respiratory frequency is commonly performed in a cursory manner and judged to be of little clinical importance. However, in a recent study of patients being weaned from mechanical ventilation, we found that tachypnea was quite accurate in predicting an unsuccessful weaning outcome. The present study was undertaken to examine the relationship between nonobtrusive measurements of respiratory frequency, using a calibrated inductive plethysmograph, and detailed measurements of pulmonary function in 11 adult patients with cystic fibrosis of varying severity. Respiratory frequency was increased in the patients with cystic fibrosis compared with a group of healthy control subjects, as was minute ventilation and mean inspiratory flow. Respiratory frequency was a sensitive predictor of respiratory dysfunction, being significantly (p less than 0.05) correlated with airway obstruction (r = 0.76), hyperinflation (r = 0.52), arterial oxygenation (r = -0.59), rib cage-abdominal discoordination (r = 0.54), and maximum ventilation during exercise (r = 0.66). Despite the presence of tachypnea, the patients did not display shallow breathing; indeed, tidal volume was not correlated with any of the above abnormalities. In conclusion, respiratory rate was a useful indicator of respiratory dysfunction in this group of patients with cystic fibrosis.

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