Paolo T. Pianosi

Peak oxygen uptake and mortality in children with cystic fibrosis

Background: Single measurements of peak oxygen uptake (V˙o2) have been shown to predict mortality in patients with cystic fibrosis (CF) although no longitudinal study of serial measurements has been reported in children. A study was undertaken to determine whether the initial, final, or the rate of fall of forced expiratory volume in 1 second (FEV1) or peak V˙o2 was a better predictor of mortality. Methods: Twenty eight children aged 8–17 years with CF performed annual pulmonary function and maximal exercise tests over a 5 year period to determine FEV1 and peak V˙o2, magnitude of their change over time, and survival over the subsequent 7–8 years. Analysis was done using Kaplan-Meier curves and Cox proportional hazard model. Results: Peak V˙o2 fell during the observation period in 70% of the patients, with a mean annual decline of 2.1 ml/min/kg. Initial peak V˙o2 was not predictive of mortality but rate of decline and final peak V˙o2 of the series were significant predictors. Patients with peak V˙o2 less than 32 ml/min/kg exhibited a dramatic increase in mortality, in contrast to those whose peak V˙o2 exceeded 45 ml/min/kg, none of whom died. The first, last, and rate of decline in FEV1 over time were all significant predictors of mortality. Conclusions: Higher peak V˙o2 is a marker for longer survival in CF patients.

Pulse oximetry in sickle cell disease.

Patients with sickle cell disease usually have mild hypoxaemia and their oxyhaemoglobin dissociation curve is shifted to the right. It follows that oxygen saturation in sickle cell disease should be lower than normal. Most subjects in this clinic had normal oxygen saturation by pulse oximetry, however. To improve the understanding of this paradox, arterialised capillary oxygen tension (PO2) and oxygen saturation were compared with simultaneously measured pulse oximeter saturation in 20 children with sickle cell disease. In addition, the PO2 at 50% haemoglobin saturation (P50) was compared with saturation measured by pulse oximetry in all 20 patients. It was found that saturation measured by pulse oximetry was, on the whole, similar to that calculated from the sampled blood. Individual deviations were not random, however, and were partly explained by differences in P50 values. It is concluded that pulse oximetry gives variable results in patients with sickle cell disease and should be used with caution to predict arterial saturation in this patient group.

Aspiration-Related Pulmonary Syndromes

Aspiration of foreign matter into the airways and lungs can cause a wide spectrum of pulmonary disorders with various presentations. The type of syndrome resulting from aspiration depends on the quantity and nature of the aspirated material, the chronicity, and the host responses. Aspiration is most likely to occur in subjects with a decreased level of consciousness, compromised airway defense mechanisms, dysphagia, gastroesophageal reflux, and recurrent vomiting. These aspiration-related syndromes can be categorized into airway disorders, including vocal cord dysfunction, large airway obstruction with a foreign body, bronchiectasis, bronchoconstriction, and diffuse aspiration bronchiolitis, or parenchymal disorders, including aspiration pneumonitis, aspiration pneumonia, and exogenous lipoid pneumonia. In idiopathic pulmonary fibrosis, aspiration has been implicated in disease progression and acute exacerbation. Aspiration may increase the risk of bronchiolitis obliterans syndrome in patients who have undergone a lung transplant. Accumulating evidence suggests that a causative role for aspiration is often unsuspected in patients presenting with aspiration-related pulmonary diseases; thus, many cases go undiagnosed. Herein, we discuss the broadening spectrum of these pulmonary syndromes with a focus on presenting features and diagnostic aspects.

Amyloidosis and exercise intolerance in ANO5 muscular dystrophy.

Anoctamin 5 and dysferlin mutations can result in myopathies with similar clinical phenotype. Amyloid deposits can occur in the muscle of patients with dysferlinopathy. We describe a 53-year-old woman with exercise intolerance since childhood, recurrent rhabdomyolysis and late-onset weakness. Muscle biopsy showed amyloid deposits within the blood vessel walls and around muscle fibers. Mutation analysis identified two pathogenic heterozygous mutations in anoctamin 5 and no mutations in dysferlin. To our knowledge this is the first report of muscle amyloidosis in anoctamin 5 muscular dystrophy. This finding suggests that patients with amyloid in muscle should be screened for anoctamin 5 muscular dystrophy.

Adolescent Fatigue, POTS, and Recovery: A Guide for Clinicians

Many teenagers who struggle with chronic fatigue have symptoms suggestive of autonomic dysfunction that may include lightheadedness, headaches, palpitations, nausea, and abdominal pain. Inadequate sleep habits and psychological conditions can contribute to fatigue, as can concurrent medical conditions. One type of autonomic dysfunction, postural orthostatic tachycardia syndrome, is increasingly being identified in adolescents with its constellation of fatigue, orthostatic intolerance, and excessive postural tachycardia (more than 40 beats/min). A family-based approach to care with support from a multidisciplinary team can diagnose, treat, educate, and encourage patients. Full recovery is possible with multi-faceted treatment. The daily treatment plan should consist of increased fluid and salt intake, aerobic exercise, and regular sleep and meal schedules; some medications can be helpful. Psychological support is critical and often includes biobehavioral strategies and cognitive-behavioral therapy to help with symptom management. More intensive recovery plans can be implemented when necessary.

Carbon Dioxide Chemosensitivity and Exercise Ventilation in Healthy Children and in Children with Cystic Fibrosis

This two-part study sought to determine the relationship between arterial Pco2, CO2 chemoresponsiveness, and ventilation during exercise in healthy children and children with cystic fibrosis (CF). In the first part, we measured the hypercapnic ventilatory response (HCVR) in 16 healthy children and 16 patients with CF, and compared HCVR with the ventilatory response to progressive exercise (Δ˙Ve/Δ˙Vco2). In the second part, we assessed the relation between age, the ventilatory equivalent for CO2 (˙Ve/˙Vco2), and arterialized capillary Pco2(Paco2), during exercise in 28 healthy children and 23 children with CF. The HCVR showed an age-related decline in both healthy controls and CF subjects. In addition, there was a correlation between forced expiratory flow from 25 to 75% of forced vital capacity and the HCVR, regardless of age. In controls, but not in CF, there was also a decline inΔ˙Ve/˙Vco2 with increasing age; and there was a significant correlation between Δ˙Ve/Δ˙Vco2 and HCVR. Findings in the second part were similar, with a significant inverse correlation between age and ˙Ve/˙Vco2 during steady state exercise only in healthy controls. However, when physiologic dead space was taken into account, both CF and healthy control children showed a significant decline in ˙Va/˙Vco2 with age. When all subjects were grouped together, there was a statistically significant correlation between Paco2 and age, such that younger subjects had lower Paco2 than older subjects. Age and Paco2 together accounted for 71% of the variance in ˙Va/˙Vco2. We conclude that younger children ventilate proportionately more on exercise than older children because they regulate Paco2 about a lower set point. As the ventilatory response to exercise is significantly correlated with the HCVR, and the latter can be reduced in the presence of airways obstruction, an innately low HCVR could permit the development of exertional hypercapnia in some CF patients with advancing pulmonary disease.

Pulmonary Function and Ventilatory Limitation to Exercise in Congenital Heart Disease

Pulmonary function in older children and adolescents following surgical repair of congenital heart disease is often abnormal for various reasons. Many of these patients report symptoms of exercise intolerance although the reason(s) for this symptom can be complicated and sometimes interrelated. Is it simply deconditioning due to inactive lifestyle, chronotropic or inotropic insufficiency? or could there indeed be ventilatory limitation to exercise? These are the questions facing the clinician with the increasing frequency of patients undergoing repair early in life and growing into adulthood. Understanding pulmonary functional outcomes and means of determining ventilatory limitation to exercise is essential to thoroughly address the problem. This article reviews pulmonary function in patients with congenital heart disease and then describes a newer technique that should be applied to determine ventilatory limitation to exercise.

Exercise Performance in Adolescents with Autonomic Dysfunction

OBJECTIVE To test the hypothesis that excessive postural tachycardia is associated with deconditioning rather than merely being an independent sign of autonomic dysfunction in patients with postural orthostatic tachycardia syndrome (POTS). STUDY DESIGN We retrospectively analyzed records from 202 adolescents who underwent both head up-tilt and maximal exercise testing. Patients were classified as POTS if they had ≥ 30 min(-1) rise in heart rate (HR) after tilt-table test; and deconditioned if peak O(2) uptake was < 80% predicted. Changes in HR during exercise and recovery were compared between groups. RESULTS Two-thirds of patients were deconditioned, irrespective of whether they fulfilled diagnostic criteria for POTS, but peak O(2) uptake among patients with POTS was similar to patients without POTS. HR was higher at rest and during exercise; whereas stroke volume was lower during exercise, and HR recovery was slower in patients with POTS compared with patients without POTS. CONCLUSIONS Most patients who presented with chronic symptoms of dizziness, fatigue, or pre-syncope, were deconditioned, but, because the proportion of deconditioned patients was similar in POTS vs non-POTS groups, we conclude that HR changes in POTS are not solely because of inactivity resulting in deconditioning.

Orthostatic Heart Rate and Blood Pressure in Adolescents: Reference Ranges

This descriptive population study of 307 public high school students, ages 15 to 17 years, was performed to establish reference ranges for orthostatic changes in heart rate and blood pressure in adolescents, and to identify influential variables. Noninvasive measurements of blood pressure and heart rate were obtained. Reference ranges for orthostatic heart rate change in this population at 2 minutes were –2 to +41 beats per minute and at 5 minutes were –1 to +48 beats per minute. Orthostatic blood pressure changes were within the adult range for 98% of adolescents tested. One-third of participants experienced orthostatic symptoms during testing. In conclusion, this study shows that orthostatic symptoms and large orthostatic heart rate changes occur in adolescents. This suggests that the current orthostatic heart rate criterion aiding the diagnosis of adult orthostatic intolerance syndromes is likely not appropriate for adolescents and should be reevaluated.

End-tidal estimates of arterial PCO2 for cardiac output measurement by CO2 rebreathing: a study in patients with cystic fibrosis and healthy controls.

We set out to determine the effects of various estimates of arterial PCO2 (PaCO2) on calculation of cardiac output (Q) by the indirect Fick (CO2) method in healthy children and children with cystic fibrosis (CF), and to develop a prediction equation for children for PaCO2, based on end‐tidal PCO2 (PetCO2). The study had 3 parts: 1) Twenty‐three healthy children exercised lightly and moderately while arterialized capillary blood gases and PetCO2 were measured simultaneously so that a prediction equation for PaCO2 could be derived from PetCO2. Cardiac output was measured by CO2 rebreathing at each workload; different values for PaCO2 (measured in arterialized capillary blood, end‐tidal, and PaCO2 derived from the Bohr equation assuming normal dead space) were used to calculate Q; 2) our equation PaCO2 = 0.647 PetCO2 + 12.4 was tested prospectively to measure Q in 9 healthy children; and 3) cardiac output based on arterialized capillary PaCO2 was compared with that based on Jones‐corrected PetCO2 during light and moderate exercise in 16 CF patients whose forced expiratory volume in 1 second (FEV1) range from normal to 37% predicted.