Inhalation of dry-powder mannitol increases mucociliary clearance

Inhalation of hypertonic saline stimulates mucociliary clearance (MCC) in healthy subjects and those with obstructive lung disease. We investigated the effect of inhaling the osmotic agent mannitol on MCC. We used a dry-powder preparation of mannitol British Pharmacopea (BP) which was encapsulated and delivered using a Dinkihaler. MCC was measured for 75 min in six asthmatic and six healthy subjects on two occasions before and after the mannitol inhalation or its control, using 99mTc-sulphur colloid and a gamma camera. The inhaled dose of mannitol was 267+/-171 mg (mean+/-SD) and 400 mg and the percentage fall in forced expiratory volume in one second (FEV1) was 22+/-3 and 4+/-2% in the asthmatic and healthy subjects, respectively. The total clearance in the whole right lung for the 60 min from the start of inhalation of mannitol was greater by 263+/-11.9% in the asthmatic and 18.1+/-4.9% in the healthy subjects compared to the control. The total clearance over 75 min was 54.7+/-9.6% and 33.6+/-9.4% on the mannitol and control day (p<0.002), respectively, in the asthmatic subjects and 40.5+/-7.1% and 24.8+/-7.8% (p<0.002) in the healthy subjects. In conclusion, inhalation of dry-powder mannitol increases mucociliary clearance in asthmatic and healthy subjects and may benefit patients with abnormal mucociliary clearance.     

Comparison of bronchial challenge with ultrasonic nebulized distilled water and hypertonic saline in children with mild-to-moderate asthma

There is still controversy about the most suitable method to measure bronchial hyperresponsiveness in children. In epidemiological surveys, nonisotonic aerosols are being used increasingly for bronchial provocation testing. Our aim was to study the acceptability, safety and correlation between two published bronchial challenge tests. Two standardized protocols--the inhalation of hypertonic saline (HS) and ultrasonically-nebulized distilled water (UNDW)--were performed in 36 children: 19 patients with the clinical diagnosis of mild-to-moderate asthma (7-12 yrs of age), and 17 control subjects (8-18 yrs of age). HS challenge involved stepwise inhalation of 4.5% saline (for 0.5, 1, 2, 4 and 8 min), whereas challenge with UNDW was performed as a single step protocol with 10 min inhalation of cold UNDW. Asthma medication was withheld prior to challenge testing. Thirty five subjects completed both challenge tests (one asthmatic patient did not return after UNDW challenge) in random order within a 7 day time interval. For HS a > or = 15% reduction in forced expiratory volume in one second (FEV1) from baseline was considered a positive response, and for UNDW a > or = 10% decrease. In 13 of the 19 asthmatic patients, but in none of the controls, a positive response was observed for UNDW. Fifteen out of 18 patients and one control subject had a positive response to HS. Twelve out of 18 asthmatic children responded to both challenges, three responded only to HS and three had no response to either challenge. There was a negative correlation between log provocative dose causing a 15% reduction in FEV1 (PD15) after HS and the maximum fall in FEV1 after UNDW (rs = -0.63; p < 0.005). The HS challenge had a lower acceptability than challenge with UNDW due to the unpleasant salty taste of HS. However, this did not inhibit the completion of the tests in any subject. The results of this study suggest a good correlation between response to hypertonic saline and ultrasonically-nebulized distilled water in children with mild-to-moderate asthma. A multiple step protocol might be safer when applied in field studies involving children.     

Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa

In this study, we examined whether mucociliary clearance differed between cystic fibrosis (CF) knockout mice and wildtype controls. Additionally, we investigated whether infection with Pseudomonas aeruginosa, a common pathogen in the CF lung, affected this important host defence mechanism. Ciliary beat frequency (fcb) and particle transport (PT) were recorded using an in vitro lung explant preparation. Measurements were made from uninfected cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-) mice and littermate controls (+/+) and compared to measurements from infected animals. While there were no differences detectable in fcb between CFTR -/- mice and their +/+ controls either in the presence or absence of P. aeruginosa, PT rates were different between these groups; interestingly, PT rates appeared dependent on both CFTR and infection status, with uninfected CFTR +/+ animals demonstrating higher rates of PT than their -/- littermates, while CFTR +/+ P. aeruginosa-infected mice demonstrated lower PT than knockout mice. These data demonstrate differences in mucociliary clearance between cystic fibrosis transmembrane conductance regulator knockout mice and controls, and further that Pseudomonas aeruginosa infection affects mucociliary clearance in the peripheral airways of mice. Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection.     

Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis

BACKGROUND: Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to which the lungs are exposed. One such group, the heat shock proteins, (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues. METHODS: Antibodies to human hsp 27 and hsp 90 in the serum of patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by bacteriological examination of sputum. RESULTS: Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibodies were higher in patients in whom the lungs were colonised with Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with arthritis had higher anti-hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). CONCLUSIONS: These findings suggest that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.     

Airway hyperresponsiveness and cough-receptor sensitivity in children with recurrent cough

In children, recurrent cough is a common presenting symptom that may represent asthma. We tested the hypotheses that children with recurrent cough have increased cough-receptor sensitivity (CRS) or airway hyperresponsiveness (AHR). Skin prick testing, the capsaicin CRS test, and hypertonic saline (HS) challenge were performed in 44 children (median age: 8.9 yr) with recurrent dry cough (> or = 2 episodes of cough, each lasting > or = 2 wk, within a period of 12 mo) and 44 controls. Measures of CRS were the concentration of capsaicin required to stimulate > or = 2 coughs (Cth) and > or = 5 coughs (C5). During the coughing period, Cth (mean log: 0.62 [95% CI: 0.43 to 0.81]) and C5 (mean log: 1.15 [95% CI: 0.86 to 1.44]) of the subjects without AHR were significantly lower (p = 0.0026, 0.027, respectively) than Cth (mean log: 1.27 [95% CI: 0.88 to 1.66]) and C5 (mean log: 1.79 [95% CI: 1.21 to 2.37]) of the subjects with AHR and those of the controls (p = 0.0002 and 0.0001). During the cough-free period, there was no difference in CRS among the groups. In subjects who demonstrated AHR, the provocation dose causing a > or = 15% fall in FEV1 (PD15) during the cough period was significantly lower (p = 0.005) than that during the cough-free period. We conclude that AHR or increased CRS is present during the coughing phase in children with recurrent cough.     

Potentiating effect of inhaled acetaldehyde on bronchial responsiveness to methacholine in asthmatic subjects

BACKGROUND: It has recently been reported that acetaldehyde induces bronchoconstriction indirectly via histamine release. However, no study has been performed to assess whether acetaldehyde worsens bronchial responsiveness in asthmatic subjects so this hypothesis was tested. METHODS: Methacholine provocation was performed on three occasions: (1) after pretreatment with oral placebo and inhaled saline (P-S day), (2) after placebo and inhaled acetaldehyde (P-A day), and (3) after a potent histamine H1 receptor antagonist terfenadine and acetaldehyde (T-A day) in a double blind, randomised, crossover fashion. Nine asthmatic subjects inhaled 0.8 mg/ml acetaldehyde or saline for four minutes. After each inhalation a methacholine provocation test was performed. RESULTS: Methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) on the P-A day (0.48 mg/ml, 95% CI 0.21 to 1.08) and T-A day (0.41 mg/ml, 95% CI 0.22 to 0.77) were lower than those on the P-S day (0.85 mg/ml, 95% CI 0.47 to 1.54). There was no change in the PC20-MCh between the P-A and T-A days. A correlation was observed between the logarithmic values of PC20-MCh (log PC20-MCh) on the P-S day and the potentiating effect of acetaldehyde on the methacholine responsiveness [(log PC20-MCh on P-A day)-(log PC20-MCh on P-S day)] (rho = 0.82). CONCLUSIONS: Acetaldehyde induces bronchial hyperresponsiveness in patients with asthma by mechanisms other than histamine release.     

Prehospital resuscitation of hypotensive trauma patients with 7.5% NaCl versus 7.5% NaCl with added dextran: a controlled trial

Small volume infusions of hypertonic saline combined with dextran are very effective in resuscitating animals that have been subjected to hemorrhagic shock, and seem to be effective in resuscitating trauma patients with severe injuries. In this study, the contribution of the dextran component was investigated in a prospective, three-armed, double-blind, randomized trial. Trauma patients transported by ambulance to the hospital with a systolic blood pressure of 90 mm Hg or less were given 250 mL of (1) normal saline (NS); (2) 7.5% NaCl (HS, for hypertonic saline); or (3) 7.5% NaCl in 6% dextran 70 (HSD). Infusion of the study solution was followed by administration of conventional isotonic fluids as the patients' conditions indicated. By predetermined hypothesis, the observed survival rates in the three treatment groups were compared with the predicted survival rates from the TRISS methodology. The 7.5% NaCl solution significantly improved upon the predicted survival for the entire cohort and for high-risk patients when compared with the survival estimates from the TRISS methodology. The addition of a colloid, in the form of 6% dextran 70, did not offer any additional benefit, at least in this setting of rapid urban transport.     

Effect of atrial natriuretic hormone on hypertonic saline-induced suppression of the renin-aldosterone system

To evaluate the effect of physiologic doses of atrial natriuretic hormone (ANH) on hypertonic saline-induced renin-aldosterone system suppression, nine healthy subjects were studied three times: 1) on a low-salt (LS) diet with a 2 h placebo infusion; 2) on LS with 2 h infusion of human Ser-Tyr28 ANH (0.6 pmol/kg/min)(LS+ANH); and 3) on a high-salt (HS) diet with a 2 h placebo infusion. On each study day during the second hour of infusion, subjects also received 3% saline (0.1 mL/kg/min) infusion. Data from eight subjects were used for analysis because of a sampling error in one subject. During ANH infusion, plasma ANH levels increased about twofold and reached levels similar to ANH levels on HS. Serum sodium increased by 3-4 mEq/L, and serum osmolality increased by 7-8 mOsm/L during 3% saline infusion on all study days. ANH levels remained stable during 3% saline infusion. During the first hour of ANH infusion, plasma renin activity (PRA) decreased by about 24% and aldosterone levels by about 27%. Hypertonic saline caused further suppression of PRA and aldosterone. The extent of the suppression was similar under each condition, and the levels at the end of hypertonic saline infusion reached about 60% of the levels at the beginning of the saline infusion. We conclude that low-dose ANH infusion does not seem to have any major influence on PRA and aldosterone response to hypertonic saline.     

Airway responsiveness to hyperosmolar saline challenge in cystic fibrosis: a pilot study

Hyperosmolar aerosols are used to assess airway responsiveness in subjects with asthma. Using a 10% NaCl aerosol, we investigated airway responsiveness in 23 cystic fibrosis (CF) subjects (12 females, 11 males; 19.1 +/- 3.3 years) who had asthma-like symptoms. The pre-challenge predicted forced expiratory volume in 1 second (FEV1) was 74.7 +/- 21.5. The aerosol was generated by a MistO2gen 143A ultrasonic nebulizer and inhaled for 0.5, 1, 2, 4, 8, 8, and 8 minutes or part thereof. Spirometry was performed before and 1 minute after each inhalation period. The challenge was stopped when a > or = 20% fall from the baseline FEV1 was recorded, after the last inhalation period, or when requested by the subject. We recorded different responses to 10% NaCl among subjects. In 7, the FEV1 fell progressively throughout the challenge in a manner similar to asthmatics. By contrast, in 15 subjects the FEV1 was higher at the completion of challenge compared to during challenge, i.e., the fall in FEV1 was transient. In 7 of these subjects, the final FEV1 at the end of the challenge was higher than the pre-challenge FEV1. We conclude that inhaled 10% hyperosmolar saline causes either progressive and sustained or transient airway narrowing during challenge in the majority of CF subjects. The cause of the transient airway narrowing requires further investigation.     

The postnatal emergence of dehydration anorexia in rats is temporally associated with the emergence of dehydration-induced inhibition of gastric emptying

Osmotic dehydration produced by systemic hypertonic NaCl (HS) inhibits gastric motility and emptying and also inhibits feeding in adult rats. Conversely, in neonatal rats, dehydration does not inhibit feeding. The present study examined whether the postnatal emergence of dehydration anorexia is temporally associated with the emergence of dehydration-induced inhibition of gastric emptying. Rat pups 4 to 19 days old were injected subcutaneously with HS (0.75 M NaCl; 200 microL/10 g body weight). Control rats were injected with isotonic saline (0.15 M NaCl). Thirty minutes later, rats were given access to milk that could be lapped from paper towels on the floor of a warm testing chamber. Other HS-treated and control rats were given an intragastric load of 0.15 M NaCl (2% body weight) and then killed after 30 min to determine how much of the load had emptied from the stomach. Consistent with previous reports, HS-treated rats consumed significantly more milk than control rats from postnatal Day 4 (P4) through P11 but consumed significantly less milk than controls at P19. HS treatment did not affect gastric emptying of 0.15 M NaCl at P4 or P11. Conversely, HS treatment significantly inhibited gastric emptying at P19. These findings suggest that the hypophagic effects of dehydration develop in tandem with inhibitory effects on gastric motility and are consistent with the view that the full complement of mature homeostatic responses to plasma hyperosmolality requires coordinated activation of forebrain and hindbrain neural circuits that are only partially formed in neonatal rats.     

Intravenous aminophylline in patients with cystic fibrosis. Pharmacokinetics and effect on pulmonary function

Intravenous aminophylline was administered to ten patients with cystic fibrosis (CF) to determine if the medication would improve pulmonary function and to study theophylline pharmacokinetics. Intravenous normal saline was given on another day as a control. Thoracic gas volume and airway resistance, measured in a volume displacement body plethysmograph, and maximal expiratory flow-volume curves were performed before and after each infusion. No significant improvement was noted in pulmonary function after normal saline infusion. Following aminophylline infusion. Following aminophylline infusion, significant improvement in thoracic gas volume, residual volume, specific airway conductance, and maximal expiratory flow at 60% of total lung capacity was noted. The pharmacokinetic analysis revealed a mean half-life of 4.7 hours, a total clearance of 91 mL/hr/kg, and a volume of distribution of 574 mL/kg. Intravenous aminophylline can acutely decrease airway obstruction in children with CF.     

How do cystic fibrosis transmembrane conductance regulator mutations produce lung disease?

In recent years, several functions of the cystic fibrosis transmembrane conductance regulator have been discovered, yet the pathophysiology of the pulmonary disease in cystic fibrosis remains unclear. At the cellular level, functions of this protein include regulation of chloride and sodium transport at the cell membrane and in intracellular organelles, regulation of protein trafficking, and posttranslational processing of glycoconjugates. Elucidation of these functions has led to several hypotheses to account for how defects in the cystic fibrosis transmembrane conductance regulator produce pulmonary disease, but a clear understanding of the pathophysiologic links between the cellular functions of the cystic fibrosis transmembrane conductance regulator and organ dysfunction has been hampered by the lack of ideal model systems. Current evidence suggests that defects in the cystic fibrosis transmembrane conductance regulator lead to alterations in periciliary fluid homeostasis, mucus hydration, mucin secretion, and apical membrane protein structure. In turn, these alterations impair mucociliary clearance and promote bacterial infection, which then leads to chronic airway inflammation and the development of bronchiectasis.     

Implications of early inflammation and infection in cystic fibrosis: a review of new and potential interventions

Airway infection and inflammation occur early in cystic fibrosis (CF) lung disease, suggesting the need for early treatment. Our current approach to routine management of CF includes a comprehensive, CF center-directed program that aims at maintaining normal nutrition and delaying the progression of lung disease. Regular secretion clearance, frequent antibiotics, and bronchodilators are commonly used. However, despite this early, aggressive comprehensive management, airway inflammation and infection progress. Several other recent approaches such as the use of corticosteroids and ibuprofen to decrease inflammation, as well as dornase alfa to thin secretions and improve pulmonary function, are under investigation in young children. Other potential treatments include amiloride/uridine triphosphate and hypertonic saline aerosol. Early treatment offers the promise of reducing morbidity as well as delaying the progression of later disease.     

Exhaled nitric oxide (NO) is reduced shortly after bronchoconstriction to direct and indirect stimuli in asthma

Exhaled NO is increased in patients with asthma and may reflect disease severity. We examined whether the level of exhaled NO is related to the degree of airway obstruction induced by direct and indirect stimuli in asthma. Therefore, we measured exhaled NO levels before and during recovery from histamine and hypertonic saline (HS) challenge (Protocol 1) or histamine, adenosine 5'-monophosphate (AMP), and isotonic saline (IS) challenge (Protocol 2) in 11 and in nine patients with mild to moderate asthma, respectively. The challenges were randomized with a 2-d interval. Exhaled NO and FEV1 were measured before and at 4, 10, 20, and 30 min after each challenge. NO was measured during a slow VC maneuver with a constant expiratory flow of (0.05 x FVC)/s against a resistance of 1 to 2 cm H2O. Baseline exhaled NO levels were not significantly different between study days in Protocol 1 (mean +/- SD: 4.8 +/- 1.8 ppb [histamine] versus 5.4 +/- 2.1 ppb [HS], p = 0.4) or in Protocol 2 (7.9 +/- 4.7 ppb [histamine], 8.3 +/- 5.2 ppb [AMP], and 7.2 +/- 3.7 ppb [IS], p = 0.7). A significant reduction in exhaled NO was observed directly after HS (mean +/- SEM: 39.2 +/- 3.9 %fall) and AMP challenge (32.3 +/- 7.3 %fall) (MANOVA, p < 0.001), respectively, whereas exhaled NO levels tended to decrease after histamine challenge. Isotonic saline challenge did not induce changes in exhaled NO (p = 0.7). There was a positive correlation between %fall in FEV1 and the %fall in exhaled NO after histamine, HS, and AMP challenge as indicated by the mean slope of the within-subject regression lines (p <= 0.04). We conclude that acute bronchoconstriction, as induced by direct and indirect stimuli, is associated with a reduction in exhaled NO levels in asthmatic subjects. This suggests that airway caliber should be taken into account when monitoring exhaled NO in asthma.     

Cystic fibrosis: effects of serum factors on mucus secretion

The effects of serum from children with cystic fibrosis and from normal children on the mucus-secreting, ciliated epithelium have been investigated in vitro using explanted tissue from rabbit lung. By optical and scanning electron microscopy, a sequence of structural changes is observed after incubation with cystic fibrosis serum; this sequence does not occur with normal serum. The earliest changes involve swelling of the goblet cells, with subsequent discharge of mucus onto the epithelial surface. This is followed by disruption of the normally rapid and synchronized ciliary activity. Mucus gradually extends over the surface entangling cilia. Finally, some shedding of ciliated cells occurs from the epithelium. These findings suggest that factors in cystic fibrosis serum cause discharge of mucus leading to a disturbance of the normal ciliary activity in the rabbit lung. It is postulated that such changes result in dysfunction of the mucociliary clearance mechanism and that this dysfunction may be a contributory factor to the pathogenesis of lung disease.     

Quality of life in adults with cystic fibrosis

BACKGROUND: Cystic fibrosis is an inherited condition with a high mortality and morbidity. The aims of this study were to assess quality of life in a population of adults with cystic fibrosis, to compare quality of life with published scores from a healthy population and other patient groups, and to examine the relation between quality of life and other measured clinical variables. METHODS: Patients over 16 years of age attending an adult cystic fibrosis outpatient clinic were surveyed at a time when they were clinically stable. A self-complete questionnaire was administered which comprised the Nottingham Health Profile (NHP) together with six additional questions related to cystic fibrosis. RESULTS: Completed questionnaires were obtained from 240 subjects (100 women) of median age 26 years (range 16-56). Mean (SD) forced expiratory volume in one second (FEV1) was 49 (26)% predicted, forced vital capacity (FVC) was 68 (26)% predicted, and the FEV1:FVC ratio was 59 (16)%. In this cross sectional study different patterns of perceived quality of life were seen in men and women. In part 1 of the NHP there was an age related trend compared with norms in men, with more distress/disability in the dimensions of emotion, sleep, and social isolation in the older age groups. In women there was no age related trend in the degree of distress/disability compared with norms. The mean score was different from norms in the dimensions of pain, emotion and sleep. For the patients with cystic fibrosis as a whole the scores in part 1 were comparable with published scores of patients with minor non-acute conditions. Scores in part 2 of the NHP for men were different from norms in six of the seven areas of daily living (all except home life). For women the scores were different from norms in the areas of looking after the home, social life, hobbies, and holidays. There were correlations between several of the quality of life dimensions and other measured variables such as FEV1, breathlessness score, and the time spent on home treatment. CONCLUSIONS: Men and women with cystic fibrosis have different patterns of perceived quality of life, and there is an age related trend of perceived quality of life in men in some dimensions. Quality of life scores in this group, as assessed by the NHP, are similar to those reported in subjects with minor non-acute conditions.     

Canine babesiosis in South Africa: more than one disease. Does this serve as a model for falciparum malaria?

The present study was carried out to determine whether the increased salt intake induce by increased specific sodium appetite in pregnant rats modifies water-salt homeostasis throughout pregnancy. Two groups of pregnant rats were used, one fed ad libitum with a normal sodium (NS) diet consisting of standard rat chow and distilled water, and the other fed with a high-sodium (HS) diet with free access to chow, distilled water plus saline solution (1.5% NaCl). Virgin rats in dioestrus were also studied as non-pregnant controls. Pregnant animals were studied on days 4, 9, 14, 20 and 21 of gestation at which time body weight, water and saline intake, sodium excretion, plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) concentrations, as well as plasma osmolality were determined. Data showed that water intake was higher in the NS group, but total fluid intake (water plus saline) was higher in the HS group throughout pregnancy. Dietary sodium intake was the same for both groups but total sodium intake (chow plus saline) was 60-98% higher in the HS rats. Pregnant HS rats excreted more fluid (35-50%) and sodium (up to 100%) compared with NS rats, indicating that the animals could change their renal excretion in response to a 2.5-fold higher dietary sodium intake compared with the control level. Salt satiety during pregnancy did not modify plasma ANP concentration. In both groups of pregnant rats ANP levels increased 3-fold on day 14 without significant alteration in sodium excretion, suggesting that the natriuretic action of ANP is attenuated at least after the second week of pregnancy. High sodium intake did not change plasma AVP concentration or osmolality and both groups showed the same gradual decrease in plasma osmolality (approximately 8 mosmol kg-1) at the end of pregnancy that was not accompanied by decreased plasma AVP concentration. The present data show that rats maintain the special homeostatic equilibrium that occurs in normal pregnancy even when they are allowed to increase sodium intake to satisfy their salt appetite during this period of the reproductive cycle.     

Changes in the pancreatic and respiratory functions in cystic fibrosis. The influence of the time of the evolution of the disease

BACKGROUND: Cystic fibrosis is the most frequent congenital disease in Caucasian and is transmitted by recessive autosomic inheritance. It is characterized by affection of different glands of exocrine secretion, particularly the pancreas and the lung. The aim of this study was to analyze the degree of alteration of pulmonary and pancreatic exocrine function in a group of patients with cystic fibrosis in relation to the time of disease evolution. METHODS: Twenty-one patients between 9 and 31 years of age were studied; 11 with an evolution of lower than or equal to 158 months and 10 with an evolution of higher than 158 months (median of the total patients). To study pancreatic exocrine function the BT-PABA test immunoreactive serum trypsin test were used. To evaluate respiratory function FEV1, FVC, FEV1/FVC ratio and PaO2 were used. RESULTS: The results obtained demonstrated that in the group with a lower time of evolution the diagnosis had been carried out at earlier ages (17 +/- 17 months versus 84 +/- 60 months; p = 0.002) and presented a significantly more altered pancreatic exocrine function (BT-PABA: 13 +/- 12% versus 35 +/- 23%; p = 0.013). However, respiratory function was altered in the group with longer time of evolution (FEV1: 68 +/- 20% versus 36 +/- 23%; p = 0.003; FVC: 74 +/- 9 versus 52 +/- 25%; p = 0.013; FEV1/FEV: 77 +/- 19 versus 50 +/- 9%; p < 0.001; PaO2: 84 +/- 16 versus 58 +/- 11%; p < 0.001). CONCLUSIONS: Pancreatic exocrine function is most intensely affected in patients diagnosed with cystic fibrosis at earlier and with shorter times of evolution while patients who have the longest time of evolution and who were diagnosed later in life presented greater changes in respiratory function.     

Clinical follow-up of an epidemiologic study on asthma and allergies in childhood

The results of a recent epidemiological study in Salzburg (Austria) showed that the prevalence of bronchial hyperresponsiveness (BHR) to hypertonic saline (HS) was 13.7% in schoolchildren aged 12-15 years. In the same study the prevalence of wheezing in the last 12 months was 11.9% and asthma had been diagnosed in 6.3%. To audit the relevance of these results and to offer medical treatment to children with newly diagnosed asthma, we invited all children who had had a positive bronchial provocation test (n = 99) or an abnormal lung function (defined as an FEV1 < 80% of the predicted value; n = 33) for clinical investigation. Seventy-five out of 99 children with BHR and 27/33 with an FEV1 < 80% of the predicted value attended the Respiratory Laboratory and a paediatric pulmonologist assessed the diagnosis on the basis of respiratory symptoms, physical examination and lung function test. In 26/53 children with asthma, the diagnosis was unknown. Although most children had mild asthma and normal lung function, half of these children had reduced physical activity. In 27/53 children with asthma, the diagnosis had already been known but, according to the specialist, had not been adequately treated. In 21/27 children with an FEV1 < 80% of the predicted value, this finding was clinically not relevant. The audit of the epidemiological study supported the assumption that asthma might be underdiagnosed and undertreated in our population.     

Ethoxycoumarin O-deethylation (ECOD) activity in rat liver slices exposed to beta-naphthoflavone (BNF) in vitro

1. To test whether cystic fibrosis (CF) altered the kinetics and dynamics of oral salbutamol, 11 patients with CF (19-33 years old; five females; FEV1: 37 +/- 12% of predicted value) and 10 healthy volunteers (20-41 years old; five females; FEV1: 99 +/- 14% of predicted value) received orally 4 mg salbutamol. 2. The estimated pharmacokinetic parameters of salbutamol in patients with CF were identical to those in healthy subjects. For instance, peak plasma concentrations of salbutamol were 10.5 +/- 2.6 (mean +/- s.d.) and 10.2 +/- 2.9 ng ml-1 (NS), and the area under salbutamol plasma concentrations as a function of time (AUC (0, 7 h)) was 43.0 +/- 9.3 ng ml-1 h and 43.3 +/- 12.7 ng ml-1 h (NS) in CF patients and in healthy subjects, respectively. Since on a mg kg-1 dose basis, CF patients received a dose 28% greater than healthy subjects, this lack of differences implies a decrease in the amount of salbutamol absorbed, or alternatively, an increase in both clearance and volume of distribution of salbutamol. 3. Salbutamol did not elicit bronchodilation in CF patients, but increased heart rate from 77 +/- 2 to 103 +/- 3 beats min-1 (P < 0.05). 4. Salbutamol decreased plasma potassium concentrations from 4.5 +/- 0.1 to 3.8 +/- 0.1 mmol l-1 in the CF group (P < 0.05) and from 4.1 +/- 0.2 to 3.4 +/- 0.1 mmol l-1 in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)