Risk factors for emergence of Stenotrophomonas maltophilia in cystic fibrosis.

The number of patients with cystic fibrosis (CF) whose sputum culture has yielded Stenotrophomonas maltophilia has increased in the last 5 years at St. Christopher's Hospital for Children. We conducted a case-control study to determine risk factors for recovery of S. maltophilia in respiratory secretions from patients with CF. We reviewed the outpatient and inpatient records of patients colonized with S. maltophilia between 1993 and 1997, and of age-matched (at time of initial recovery of S. maltophilia) control patients with CF who had never had a positive sputum culture for S. maltophilia. Variables included age at time of CF diagnosis, gender, severity of CF (based on Shwachman-Kulczycki (S-K) scores and spirometry), frequency of hospitalizations, use of oral, intravenous, or inhaled antibiotics, and use of oral or inhaled corticosteroids in the 2 years prior to the first isolation of S. maltophilia from respiratory secretions. Statistical methods included stepwise logistic regression to determine risk factors for acquisition of S. maltophilia. During the study period, 58 patients with CF had a positive sputum or deep throat culture for S. maltophilia. The distribution of S. maltophilia acquisition by year increased from 7 patients in 1993 (incidence, 2.8%) to 16 in 1997 (incidence, 6.2%). Patients positive for S. maltophilia were found to have significantly worse growth parameters, S-K score, and spirometric values than S. maltophilia-negative CF controls (P < 0.05). Stepwise logistic regression demonstrated that treatment with long-term antibiotics (P = 0.0016) and number of days of intravenous antibiotic therapy (P = 0.035) were significant risk factors for S. maltophilia colonization in our group of CF patients. We conclude that patients with CF whose respiratory secretions yield S. maltophilia have an overall worse clinical status at the time of initial S. maltophilia isolation than noncolonized patients, and that preceding treatment with antibiotics may have predisposed them to the acquisition of this bacterium in their respiratory secretions.

Mechanisms of nocturnal oxyhemoglobin desaturation in children and adolescents with sickle cell disease.

Oxyhemoglobin desaturation in patients with sickle cell disease has been proposed as a possible mechanism in the initiaton of vasco-occlusive pain crises. Nocturnal oxyhemoglobin desaturation (NOD) has been described with a prevalence of up to 40% in children and adolescents with sickle cell disease. The objective of this study was to evaluate the mechanisms of nocturnal oxyhemoglobin desaturation in sickle cell disease and determine the role of obstructive sleep apnea. We performed 16-channel polysomnograms and pulmonary function testing in 20 patients with sickle cell disease (ages 7-21 years) who had documented desaturation on home oximetry studies. The median saturation awake was 94% (quartile range, 88-95). Median saturation during REM sleep was 93.5% (88-95) and during non-REM sleep 93.5% (87.5-95). The median respiratory disturbance index was low (1.35 quartile range, 0.25-2.85). Twelve patients had no obstructive apnea recorded, while 3 patients had a total of 9 or 10 episodes during the entire study. The median snoring time was 5. 65% of total sleep time (quartile range, 1.35-22.65). There was no correlation between number of obstructive apneas and mean sleeping saturation (r = 0.012, p = 0.95). There was no correlation between pulmonary function data and prevalence of NOD. There was a strong, positive correlation between sleeping and awake saturation (r = 0.96, p < 0.001). We conclude that while nocturnal oxyhemoglobin desaturation may be common in children and adolescents with sickle cell disease, upper airway obstruction does not appear to play an important role in its genesis.

Measurement of hemoglobin saturation by oxygen in children and adolescents with sickle cell disease.

Pulse oximetry is a noninvasive method of measuring oxyhemoglobin saturation. The validity of pulse oximetry in sickle cell disease (SCD) has been questioned. We evaluated pulse oximetry, arterial blood gas analysis, and co-oximetry in patients with SCD, and we assessed the effect of dyshemoglobin and altered blood-oxygen affinity on their accuracy. Sixteen patients with SCD aged 7-21 years had arterial and venous blood drawn and transcutaneous pulse oximetry performed. Oxyhemoglobin dissociation curves were plotted from the venous blood of 15 patients. Oxyhemoglobin saturation estimated by arterial blood gas analysis (SaO(2)) and measured by pulse oximetry (SpO(2)) were both higher than the saturation by co-oximetry (FO(2)Hb) (mean +/- SD = 96.3 +/- 1.6%, 94 +/- 3.1%, and 89.1 +/- 3.8%, respectively). There was a significant, positive correlation between SpO(2) and FO(2)Hb (r = 0.7, P = 0.002). The patients had elevated levels of methemoglobin (MetHb) and carboxyhemoglobin (COHb) (2.3 +/- 1.4% and 4.7 +/- 1.3%, respectively). The oxyhemoglobin dissociation curves were frequently shifted to the right with oxygen tensions elevated when hemoglobin was 50% saturated with oxygen (P(50)) (32.5 +/- 4.5 mm Hg). There was a strong correlation between the amounts of dyshemoglobin (MetHb + COHb) and the difference between SaO(2) and FO(2)Hb (r = 0.7, P = 0.002). There was no correlation between the difference between SaO(2) and FO(2)Hb and the P(50) (r = 0.27, P = 0.33) There was also a strong positive correlation between SaO(2)-SpO(2) and dyshemoglobin fraction (r = 0.77, P = 0.001). We conclude that pulse oximetry and arterial blood gas analysis overestimate oxygen saturation when compared to co-oximetry, but that SpO(2) is consistently closer than SaO(2) to FO(2)Hb. SpO(2) is partially affected by MetHb and COHb. The discrepancy between SaO(2) and FO(2)Hb is due to the presence of dyshemoglobin and a shifted oxyhemoglobin dissociation curve, but the effect from dyshemoglobin predominates.

Management and care of the newly diagnosed patient with cystic fibrosis.

Cystic fibrosis is the most common autosomal recessive fatal disease among whites. Life expectancy is now at 31 years of age. The major cause of morbidity and mortality is chronic progressive lung disease. Lung disease occurs early in cystic fibrosis, suggesting the need for early and aggressive treatment of any pulmonary symptoms and malnutrition. This treatment is ideally performed within a cystic fibrosis center, and new therapies are being sought for management of the early stages of disease.

Airway hyperreactivity in children with sickle cell disease.

Progressive restrictive defect with increasing age, obstructive lung disease, and bronchodilator responsiveness have been reported in sickle cell disease (SCD). Because airway hyperreactivity (AHR) can be underestimated when assessed by bronchodilator responsiveness in patients with normal baseline lung function, the aim of this study was to investigate the prevalence of AHR in SCD by cold-air bronchial provocation testing, and to assess whether AHR can be present in symptom-free patients with SCD. Forty patients aged 6 to 19 years (mean, 10.7 years +/- 3.5 SD) performed pulmonary function tests. Eighteen were known to have a history of reactive airway disease (RAD group), and 22 had no known history of RAD (non-RAD group). A control group, aged 6 to 7 years (mean, 10.5 +/- 3.1 years), consisted of 10 siblings of the non-RAD SCD group. There were no significant differences in age and height among the groups. If the forced expiratory volume in 1 second (FEV1) was greater than 70%, cold air challenge (CACh) was performed; if the FEV1 was less than 70%, aerosolized bronchodilator therapy was given. A decrease in FEV1 of more than 10% after CACh or an increase in FEV1 of 12% or greater after bronchodilator inhalation was considered evidence of AHR. In the RAD group, the total lung capacity was 88.9% +/- 14.0% of race-corrected predicted values, the forced vital capacity was 91.2% +/- 12.6%, and FEV1 was 85.3% +/- 16.2%. The mean maximal percent fall in FEV1 after CACh (n = 13) was 18.5% +/- 9.6% and was greater than 10% in 11 of 13 patients. The mean increase in FEV1 after bronchodilator therapy (n = 5) was 11.5% +/- 8.3%, and it was greater than 12% in 4 of 5 patients. In the non-RAD group the baseline total lung capacity was 101.6% +/- 11.7%, forced vital capacity was 95.5% +/- 10.2%, and FEV1 was 93.3% +/- 13.2%. The mean maximal percent fall in FEV1 after CACh (n = 19) was 14.1% +/- 8.8% and was greater than 10% in 13 of 19 patients. The mean increase in FEV1 after bronchodilator therapy (n = 3) was 14.7% +/- 11.3%, and was 12% of greater in 1 of 3 patients. In the control group the baseline total lung capacity was 105.7% +/- 12.1%, forced vital capacity was 96.2% +/- 11.1%, and FEV1 was 92.9% +/- 10.3%. The mean maximal percent fall in FEV1 was 5.0% +/- 2.5%, and was greater than 10% in none of 10 patients. The prevalence of AHR in the control group, the RAD group, and the non-RAD group was zero, 83%, and 64%, respectively (p < 0.0001). The overall prevalence in the SCD group was 73%. We conclude that there is a high prevalence of AHR in children with SCD and that airway hyperreactivity may exist in patients with SCD even in the absence of the clinical symptoms of RAD. AHR may be a significant component of sickle cell lung disease.

Maturation of catecholamine response and extraneuronal uptake in rabbit trachea.

The present study investigated whether maturational changes in extraneuronal catecholamine clearance accounted for the ontogenetic attenuation of isoproterenol responsiveness in rabbit tracheal segments. Following half-maximal contraction with acetylcholine (ACh) or KCl, tracheal ring segments (TS) isolated from newborn, 1-mo, and adult rabbits were relaxed with cumulative administration of isoproterenol. With postnatal maturation, there occurred a significant decrease in both maximal relaxation and sensitivity to isoproterenol in both ACh- and KCl-contracted TS. Inhibition of extraneuronal catecholamine uptake with methylprednisolone resulted in enhanced sensitivity to isoproterenol in 1-mo and adult, but not in newborn tracheal segments. In separate studies, extraneuronal catecholamine uptake was directly assayed in tracheal segments isolated from rabbits of similar age and pretreated with neuronal uptake and monoamine oxidase inhibitors. Maximal extraneuronal uptake of [3H]norepinephrine significantly decreased with age in tracheal tissues. In contrast, the sensitivity of the uptake process to norepinephrine increased with age. The relative catecholamine reserve markedly decreased with age in rabbit tracheal segments and was directly related to the maximal degree of relaxation elicited with the beta-adrenergic catecholamine, isoproterenol, in age-matched TS precontracted with either ACh or KCl. These findings suggest that, with maturation, extraneuronal uptake more effectively competes with beta-adrenoreceptor stimulation and, accordingly, may contribute to the ontogenetic attenuation of beta-adrenergic responsiveness in rabbit tracheal tissues.