Nocturnal hypoxaemia is associated with adverse outcomes in interstitial lung disease.

BACKGROUND AND OBJECTIVE: Sleep-disordered breathing (SDB) has been reported as highly prevalent in idiopathic pulmonary fibrosis (IPF) and other interstitial lung disease (ILD) populations. Nocturnal oxygen desaturation (NOD), or the total sleep time spent with SpoO2 < 90% (TST < 90), can occur both with and without associated apnoeas, and is common in ILD. This study aimed to characterize abnormal SDB and extent of TST < 90 in ILD patients and evaluate relationships between TST < 90 and markers of disease severity, development of pulmonary hypertension (PH) and mortality. METHODS: Consecutive, newly referred ILD patients attending a specialist clinic underwent polysomnography (PSG). Serial lung function tests, echocardiography and other clinical variables were recorded. Predictors of PH and mortality were evaluated using logistic regression and Cox proportional hazards regression analyses. RESULTS: A total of 92 ILD patients (including 44 with IPF) underwent PSG. At least mild obstructive sleep apnoea (OSA) was observed in 65.2%, with rapid eye movement (REM)-related events occurring frequently. At least 10% TST < 90 (designated 'significant NOD') was present in 35.9% of patients, and was associated with PH at baseline echocardiography. Multiple indices of hypoxaemia during sleep, including significant NOD, predicted the development of new or worsening PH. TST < 90 predicted overall and progression-free survival. CONCLUSION: Nocturnal oxygen saturation is associated with poorer prognosis in ILD patients and may contribute towards the pathogenesis of pulmonary vascular disease.

Exercise pathophysiology and the role of oxygen therapy in idiopathic interstitial pneumonia.

Exercise limitation is a common feature in idiopathic interstitial pneumonia (IIP). There are multiple contributing pathophysiological mechanisms, including ventilatory mechanical limitation, impaired gas exchange, pulmonary vascular insufficiency and peripheral muscle dysfunction. Progressive exertional dyspnoea and functional incapacity impact significantly on quality of life. Exercise-induced desaturation is frequently observed and is predictive of poorer outcomes. Tests to assess the cardiorespiratory system under stress (e.g. cardiopulmonary exercise testing and the 6-min walk test) can provide important physiologic and prognostic information as adjuncts to resting measurements of lung function. Despite many advances in understanding disease mechanisms, therapies to improve exercise capacity, symptom burden and quality of life are lacking. Exercise training and supplemental oxygen are two potential interventions that require closer evaluation in patients with IIP.

Exercise capacity and stroke volume are preserved late after tetralogy repair, despite severe right ventricular dilatation.

OBJECTIVES: To assess if exercise capacity and resting stroke volume are different in tetralogy of Fallot (TOF) repair survivors with indexed RV (right ventricle) end-diastolic volume (RVEDVi) more versus less than 150 ml/m(2), a currently suggested threshold for pulmonary valve replacement (PVR). DESIGN: Cross-sectional study. SETTING: Single-centre adult congenital heart disease unit. PATIENTS: 55 consecutively eligible patients with repaired TOF (age at repair 2.3±1.9 years; age at evaluation 26.2±8.8 years; NYHA Class I or II). INTERVENTIONS: Cardiovascular MRI (1.5T) and cardiopulmonary exercise test. MAIN OUTCOME MEASURES: Biventricular volumes and function; exercise capacity. RESULTS: 20 patients had RVEDVi below, and 35 had RVEDVi above 150 ml/m(2), at time of referral. In the >150 ml/m(2) group, fractional pulmonary regurgitation was higher (41±8 vs 31±8%, p<0.001). Although RV ejection fraction (EF) was lower (47±7 vs 54±6%, p=0.007), indexed RV stroke volume was higher (87±14 vs 64±10 ml/m(2), p<0.001) in the >150 ml/m(2) group. There were no significant differences in LVEF, indexed LV stroke volume or exercise capacity (% predicted peak work: 90±17 vs 89±11% and; % predicted VO(2) peak: 84±17 vs 87±12%). CONCLUSIONS: Exercise capacity and stroke volume are maintained with RVEDVi above compared with below a commonly used cut-off for PVR surgery. Optimal timing for PVR, thus, remains unclear.

Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma.

The regional pattern and extent of airway closure measured by three-dimensional ventilation imaging may relate to airway hyperresponsiveness (AHR) and peripheral airways disease in asthmatic subjects. We hypothesized that asthmatic airways are predisposed to closure during bronchoconstriction in the presence of ventilation heterogeneity and AHR. Fourteen asthmatic subjects (6 women) underwent combined ventilation single photon emission computed tomography/computed tomography scans before and after methacholine challenge. Regional airway closure was determined by complete loss of ventilation following methacholine challenge. Peripheral airway disease was measured by multiple-breath nitrogen washout from which S(cond) (index of peripheral conductive airway abnormality) was derived. Relationships between airway closure and lung function were examined by multiple-linear regression. Forced expiratory volume in 1 s was 87.5 ± 15.8% predicted, and seven subjects had AHR. Methacholine challenge decreased forced expiratory volume in 1 s by 23 ± 5% and increased nonventilated volume from 16 ± 4 to 29 ± 13% of computed tomography lung volume. The increase in airway closure measured by nonventilated volume correlated independently with both S(cond) (partial R(2) = 0.22) and with AHR (partial R(2) = 0.38). The extent of airway closure induced by methacholine inhalation in asthmatic subjects is greater with increasing peripheral airways disease, as measured by ventilation heterogeneity, and with worse AHR.

Iatrogenic osteoporosis, bilateral HIP osteonecrosis, and secondary adrenal suppression in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted highly active antiretroviral therapy.

OBJECTIVE: To report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy. METHODS: We describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature. RESULTS: A 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy. Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma. CONCLUSIONS: Given the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavir-boosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression.

Sodium cromoglycate and eformoterol attenuate sensitivity and reactivity to inhaled mannitol in subjects with bronchiectasis.

BACKGROUND AND OBJECTIVE: Dry powder mannitol has the potential to be used to enhance clearance of mucus in subjects with bronchiectasis. A reduction in FEV1 has been recorded in some subjects with bronchiectasis after inhaling mannitol. The aim of this study was to investigate if pre-medicating with either sodium cromoglycate (SCG) or eformoterol could inhibit this reduction in FEV1. METHODS: A double-blind, placebo-controlled, randomized cross-over study was conducted. Lung function and airway response to mannitol was assessed on a control day and then re-assessed after pre-medication with placebo, SCG and eformoterol in nine subjects. Sensitivity to mannitol, expressed as the dose required to induce a 15% fall in FEV1 (PD15), and reactivity to mannitol, expressed as the % fall in FEV1 per mg of mannitol (response-dose ratio, RDR), are reported. RESULTS: Subjects had an FEV1 of 68 ± 14% predicted, FVC of 97 ± 15% predicted and FEV1 /FVC of 71 ± 8%. They were mildly hypoxemic and the SpO2 was 95 ± 2%.They had a PD15 to mannitol of 235 mg (95% CI: 150-368 mg) and a RDR of 0.057% fall in FEV1 per mg (95% CI: 0.038-0.085). After pre-medication with SCG, PD15 increased (773 mg, P < 0.05) and RDR was reduced (0.013, P < 0.05). Pre-medication with eformoterol also resulted in an increased PD15 (1141 mg, P < 0.01) and a reduced RDR (0.009, P < 0.01). A small but significant decrease in SpO2 from baseline was noted after mannitol in the presence of SCG (P < 0.05). CONCLUSIONS: Pre-medication with either SCG or eformoterol protects patients with bronchiectasis from developing a significant reduction in FEV1 after inhaling mannitol.

Gas exchange in disease: asthma, chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung disease.

Ventilation-perfusion (VA/Q) inequality is the underlying abnormality determining hypoxemia and hypercapnia in lung diseases. Hypoxemia in asthma is characterized by the presence of low VA/Q units, which persist despite improvement in airway function after an attack. This hypoxemia is generally attenuated by compensatory redistribution of blood flow mediated by hypoxic vasoconstriction and changes in cardiac output, however, mediator release and bronchodilator therapy may cause deterioration. Patients with chronic obstructive pulmonary disease have more complex patterns of VA/Q inequality, which appear more fixed, and changes in blood flow and ventilation have less benefit in improving gas exchange efficiency. The inability of ventilation to match increasing cardiac output limits exercise capacity as the disease progresses. Deteriorating hypoxemia during exacerbations reflects the falling mixed venous oxygen tension from increased respiratory muscle activity, which is not compensated by any redistribution of VA/Q ratios. Shunt is not a feature of any of these diseases. Patients with cystic fibrosis (CF) have no substantial shunt when managed according to modern treatment regimens. Interstitial lung diseases demonstrate impaired oxygen diffusion across the alveolar-capillary barrier, particularly during exercise, although VA/Q inequality still accounts for most of the gas exchange abnormality. Hypoxemia may limit exercise capacity in these diseases and in CF. Persistent hypercapnic respiratory failure is a feature of advancing chronic obstructive pulmonary disease and CF, closely associated with sleep disordered breathing, which is not a prominent feature of the other diseases. Better understanding of the mechanisms of hypercapnic respiratory failure, and of the detailed mechanisms controlling the distribution of ventilation and blood flow in the lung, are high priorities for future research.

Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial.

BACKGROUND: Palliative oxygen therapy is widely used for treatment of dyspnoea in individuals with life-limiting illness who are ineligible for long-term oxygen therapy. We assessed the effectiveness of oxygen compared with room air delivered by nasal cannula for relief of breathlessness in this population of patients. METHODS: Adults from outpatient clinics at nine sites in Australia, the USA, and the UK were eligible for enrolment in this double-blind, randomised controlled trial if they had life-limiting illness, refractory dyspnoea, and partial pressure of oxygen in arterial blood (PaO(2)) more than 7.3 kPa. Participants were randomly assigned in a 1:1 ratio by a central computer-generated system to receive oxygen or room air via a concentrator through a nasal cannula at 2 L per min for 7 days. Participants were instructed to use the concentrator for at least 15 h per day. The randomisation sequence was stratified by baseline PaO(2) with balanced blocks of four patients. The primary outcome measure was breathlessness (0-10 numerical rating scale [NRS]), measured twice a day (morning and evening). All randomised patients who completed an assessment were included in the primary analysis for that data point (no data were imputed). This study is registered, numbers NCT00327873 and ISRCTN67448752. FINDINGS: 239 participants were randomly assigned to treatment (oxygen, n=120; room air, n=119). 112 (93%) patients assigned to receive oxygen and 99 (83%) assigned to receive room air completed all 7 days of assessments. From baseline to day 6, mean morning breathlessness changed by -0.9 points (95% CI -1.3 to -0.5) in patients assigned to receive oxygen and by -0.7 points (-1.2 to -0.2) in patients assigned to receive room air (p=0.504). Mean evening breathlessness changed by -0.3 points (-0.7 to 0.1) in the oxygen group and by -0.5 (-0.9 to -0.1) in the room air group (p=0.554). The frequency of side-effects did not differ between groups. Extreme drowsiness was reported by 12 (10%) of 116 patients assigned to receive oxygen compared with 14 (13%) of 108 patients assigned to receive room air. Two (2%) patients in the oxygen group reported extreme symptoms of nasal irritation compared with seven (6%) in the room air group. One patient reported an extremely troublesome nose bleed (oxygen group). INTERPRETATION: Since oxygen delivered by a nasal cannula provides no additional symptomatic benefit for relief of refractory dyspnoea in patients with life-limiting illness compared with room air, less burdensome strategies should be considered after brief assessment of the effect of oxygen therapy on the individual patient. FUNDING: US National Institutes of Health, Australian National Health and Medical Research Council, Duke Institute for Care at the End of Life, and Doris Duke Charitable Foundation.

Beneficial effect of inhaled mannitol and cough in asthmatics with mucociliary dysfunction.

Asthmatics with overproduction of mucus that is viscous and sticky have impaired mucociliary clearance (MCC) leading to mucus plugs, and airway obstruction. Inhaled mannitol improves mucus clearance in other hypersecretory diseases. This study investigated the effect of mannitol and cough in asthmatics with mucociliary dysfunction. Seven stable asthmatics, age 52 ± 20 yr, lifelong non-smokers, without the diagnosis of bronchiectasis, with chronic cough and sputum production, treated with inhaled corticosteroids participated in the study. MCC and cough clearance (CC) was measured on 4 visits: at baseline (no cough or mannitol), with mannitol (240 and 480 mg) and cough control (no mannitol) over total 90 min using a radioaerosol technique and imaging with a gamma camera. Cough clearance was assessed after MCC by asking subjects to cough 100 times over 30 min. Premedication with eformoterol (12 µg) on all visits protected all subjects from bronchoconstriction (fall in FEV(1) > 15%) in response to mannitol. Mean (±SD) clearance over 60 min increased from 5.5 ± 5.6% at baseline and 7.3 ± 6.6% with cough control to 19.5 ± 14.6% and 26.4 ± 11.5% with 240 mg (p < 0.003) and 480 mg (p < 0.0001) of mannitol respectively. Total clearance (MCC + CC) over 90 min increased from 6.9 ± 6.5% (baseline) and 12.6 ± 8.3% without mannitol (cough control) to 34.6 ± 13.5 and 36.6 ± 10.4% with 240 and 480 mg mannitol respectively (p < 0.0001). Clearance over 90 min at baseline was not significantly different to cough control (p > 0.05). Mannitol improved clearance in all lung regions (p < 0.005). In conclusion, mannitol improved both mucociliary and cough clearance in asthmatics with mucociliary dysfunction and ineffective cough clearance. Clinical Trial registered with www.anzctr.org.au; Number ACTRN 12609001066279.aspx.

Effect of mannitol and repetitive coughing on the sputum properties in bronchiectasis.

UNLABELLED: Mucociliary clearance increases with increasing doses of mannitol and clearance is enhanced when mannitol inhalation is followed by repetitive voluntary coughing. The aim of the study was to investigate: 1) the effect of increasing doses of mannitol and repetitive coughing on the sputum physical properties; 2) if the changes in sputum properties can predict the efficacy of mucus clearance measured by radioaerosol technique in bronchiectasis patients. Sputum was collected from 14 patients, age: 63+/-6yr, who participated on the mucociliary and cough clearance studies at baseline, with mannitol (160, 320 and 480mg) and control (Daviskas et al. ERJ 2008; 31:765-772). Sputum was collected: 1) on the screening visit before and after mannitol challenge (635mg); 2) at the start and end of each clearance study after 100 repetitive voluntary coughs except on the control study (no mannitol or repetitive coughing). The sputum solids content, surface tension, contact angle and rheology were measured. Mannitol in association with coughing and coughing alone reduced the solids content, surface tension, contact angle and viscoelastic sputum properties (p<0.0001) and this effect, unlike mucociliary clearance, was not dose dependent. The control produced no effect. Total mucus clearance correlated only with the percentage reduction in surface tension on 480mg mannitol and with the reduction in solids content at baseline. IN CONCLUSION: Inhaled mannitol and voluntary repetitive coughing improved the sputum physical properties in bronchiectasis patients and this effect was not dose dependent. Changes in sputum properties do not predict efficacy of mucociliary and cough clearance.

Gas exchange in stable patients with moderate-to-severe lung disease from cystic fibrosis.

BACKGROUND: Studies using the multiple inert gas elimination technique (MIGET) to characterise the mechanisms of impaired gas exchange in CF, provide conflicting results on the importance of ventilation-perfusion (VA/Q) inequality over shunt. We hypothesise that the mechanisms of gas exchange abnormality have changed with changing CF management over the last two decades. METHODS: Detailed gas exchange was evaluated by MIGET with venous sampling in stable patients, age > 20 years, FEV1% predicted < or = 50. RESULTS: Fifteen (14 male) subjects were studied with a mean +/- SD age 28.1 +/- 8.4 years, FEV1% 32.6 +/- 10.3, TLC% 111.5 +/- 12.9, PaO2 9.3 +/- 1.3 kPa, (69.5 +/- 9.6 mm Hg), and PaCO2 6.2 +/- 0.7 kPa, (45.9 +/- 5.3 mm Hg). The predominant gas exchange abnormality was VA/Q inequality with a log SD of the distributions of perfusion 0.91 +/- 0.30 and of ventilation 0.60 +/- 0.14. Unimodal distributions were seen in nine subjects, a low VA/Q mode in five and one subject had a bimodal distribution, mean intrapulmonary shunt was negligible. CONCLUSIONS: Subjects had a lower FEV1% by comparison with previously published studies and demonstrated severe VA/Q inequality and negligible shunt. This suggests a low degree of complete obstruction of airways in adults with CF and severe stable pulmonary disease. The primary mechanism of hypoxaemia in CF subjects reaching adulthood today appears to have changed with modern management over the last two decades.

Pulmonary gas exchange response to exercise- and mannitol-induced bronchoconstriction in mild asthma.

Both exercise (EIB) and mannitol challenges were performed in asthmatic patients to assess and compare their pulmonary gas exchange responses for an equivalent degree of bronchoconstriction. In 11 subjects with EIB [27 +/- 4 (SD) yr; forced expiratory volume in 1 s (FEV(1)), 86 +/- 8% predicted], ventilation-perfusion (Va/Q) distributions (using multiple inert gas elimination technique) were measured 5, 15, and 45 min after cycling exercise (FEV(1) fall, 35 +/- 12%) and after mannitol (33 +/- 10%), 1 wk apart. Five minutes after EIB, minute ventilation (Ve; by 123 +/- 60%), cardiac output (Qt, by 48 +/- 29%), and oxygen uptake (Vo2; by 54 +/- 25%) increased, whereas arterial Po2 (Pa(O2); by 14 +/- 11 Torr) decreased due to moderate Va/Q imbalance, assessed by increases in dispersions of pulmonary blood flow (log SD(Q); by 0.53 +/- 0.16) and alveolar ventilation (log SD(V); by 0.28 +/- 0.15) (dimensionless) (P < 0.01 each). In contrast, for an equivalent degree of bronchoconstriction and minor increases in Ve, Qt, and Vo2, mannitol decreased Pa(O2) more intensely (by 24 +/- 9 Torr) despite fewer disturbances in log SDQ (by 0.27 +/- 0.12). Notwithstanding, mannitol-induced increase in log SDV at 5 min (by 0.35 +/- 0.15) was similar to that observed during EIB, as was the slow recovery in log SD(V) and high Va/Q ratio areas, at variance with the faster recovery of log SD(Q) and low Va/Q ratio areas. In asthmatic individuals, EIB provokes more Va/Q imbalance but less hypoxemia than mannitol, primarily due to postexercise increases in Ve and Qt benefiting Pa(O2). Va/Q inequalities during both challenges most likely reflect uneven airway narrowing and blood flow redistribution generating distinctive Va/Q patterns, including the development of areas with low and high Va/Q ratios.

Quantifying amount of adsorption of levothyroxine by percutaneous endoscopic gastrostomy tubes.

BACKGROUND: It has been the authors' clinical experience that hypothyroid patients who achieve a euthyroid state on a steady dose of oral levothyroxine often become hypothyroid over time if the medication is given via a feeding tube. The authors hypothesize that the tubing and enteral feeds may adsorb a significant percentage of the levothyroxine and thereby reduce its bioavailability. To the authors' knowledge, no previous research has been reported on this subject. They therefore performed an in vitro assessment of the degree of levothyroxine adsorption to quantify the amount of drug adsorbed to the percutaneous endoscopic gastrostomy (PEG) tube and how enteral tube feeds mitigate or exacerbate this adsorption. METHODS: Using levothyroxine radiolabeled with an I 125 tracer, a known dose of levothyroxine was passed through 60 new PEG tubes. One-half of the tubes were pretreated with Jevity feeds, and the other half were not. The authors measured the activity of the radiolabeled levothyroxine before and after it had passed through the tubes and, using a subtraction analysis, inferred the amount of thyroxine left within the tube. RESULTS: Tubes presoaked with feeds had a greater uptake in radioactivity by 326.4 cpm (95% confidence interval, 226.7-426.1), corresponding to a 45.08% relative increase in uptake compared with virgin PEG tubes without feeds. CONCLUSIONS: Although the authors found statistically significant differences in mean drug concentrations, they conclude that the amount of uptake of levothyroxine by PEG tubes and adsorption of levothyroxine by PEG tubes is probably clinically insignificant. The differences found may be attributed to the amount of drug lost during crushing and transfer.

Electroencephalographic arousals during sleep do not alter the pressor response to Cheyne-Stokes respiration in subjects with chronic heart failure.

This study examined the influence of electroencephalographic (EEG) arousal on the magnitude and morphology of the pressor response to Cheyne-Stokes respiration (CSR) in subjects with congestive heart failure (CHF). Thirteen subjects with stable CHF (left ventricular ejection fraction, 26 +/- 7%) and CSR (apnea-hypopnea index 52 +/- 15 h(-1)) underwent overnight polysomnography with beat-to-beat measurement of systemic arterial blood pressure (BP). CSR events were divided into those with or without an EEG arousal defined according to the criteria of the American Sleep Disorders Association. The pressor response was quantified in terms of the delta BP change (difference between the minimum BP during apnea and maximum BP during hyperpnea). Changes in the morphology of the pressor response were assessed by subdividing individual respiratory events into six periods (three during apnea: A1, A2, A3; and three during hyperpnea: H1, H2, H3). Considerable fluctuations in BP and heart rate (HR) were observed across the CSR cycle (delta mean BP 20.2 +/- 6.5 mmHg). The presence of an EEG arousal did not alter the amplitude of fluctuations in BP. Mean blood pressure (MBP) increased 21.0 +/- 7.5 mmHg with arousal versus 19.3 +/- 5.8 mmHg without arousal (NS). A repeated measures ANOVA showed no significant interaction between the presence of arousal and the proportional change in mean BP across the six periods, indicating that an EEG arousal had no effect on the morphology of MBP change during CSR [F(5,60) = 1.44, P = 0.22]. This study showed that EEG-defined arousal does not amplify the pressor response to CSR in CHF.

Inhaled mannitol changes the sputum properties in asthmatics with mucus hypersecretion.

BACKGROUND AND OBJECTIVES: Most asthmatics with mucus hypersecretion have difficulty in clearing their secretions so that mucus plugs and airway obstruction are commonly present. Inhaled mannitol facilitates clearance of mucus. This study investigated the changes in the physical properties of sputum in response to mannitol in asthmatics with chronic cough and sputum production. METHOD: Sputum was collected from 12 asthmatics (26-73 year), lifelong non-smokers, at baseline, after eformoterol (24 mug) and after mannitol on each of four visits. Inhaled mannitol doses were: 635 mg (Visit 1), 240 mg (Visit 2), 360 mg (Visit 3) and 360 mg in the presence of montelukast (Visit 4). Eformoterol was inhaled before mannitol on each visit to prevent bronchoconstiction. Sputum measurements included viscosity, elasticity, surface tension, contact angle-glass and percentage solids. RESULTS: There were no significant differences between the sputum properties at baseline and after eformoterol. Mannitol (360 mg) reduced the baseline (mean +/- SEM) elasticity from 29.9 +/- 4.5 to 15.1 +/- 1.4 Pa (P < 0.0001), viscosity from 18.4 +/- 3.2 to 8.1 +/- 1.2 Pa (P < 0.0001) at 1 rad/ s, surface tension from 92.1 +/- 2.2 to 81.9 +/- 2.5 mN/m (P < 0.0001), contact angle-glass from 57.5 +/- 3.2 to 49.6 +/- 2.0 degrees (P < 0.0001), and percentage solids from 6.9 +/- 0.7 to 5.7 +/- 0.4% (P < 0.0001). All doses of mannitol reduced the sputum properties similarly and no property was further reduced by montelukast (P > 0.4). CONCLUSION: Inhaled mannitol reduced the viscoelasticity, surface tension, contact angle and the solids content of sputum in asthmatics with chronic cough and sputum production, consistent with the osmotic effect of mannitol causing water efflux in the airway lumen.

Mucociliary clearance in patients with chronic asthma: effects of beta agonists.

OBJECTIVE: Chronic asthma is characterized by airway inflammation, mucus hypersecretion and impaired mucociliary clearance (MCC). We investigated baseline MCC and the acute effect of terbutaline in chronic asthmatics with sputum production while on long-term treatment with salmeterol in combination with inhaled corticosteroids (ICS). METHODOLOGY: MCC was measured at baseline and in response to 1 mg terbutaline (or placebo) on three visits over 80 min in 16 asthmatics (52+/-13 years of age). Subjects who had greater than 10% absolute increase in MCC above baseline and placebo, after terbutaline, were categorized in group A and subjects who had less than 10% in group B. RESULTS: In group A subjects (n=6), MCC increased from 23.7+/-4.0% at baseline to 43.7+/-4.9% with terbutaline (P<0.0001) and to 34.4+/-5.7% with placebo (P<0.01). In group B subjects (n=10), MCC remained similar: 11.3+/-3.2% at initial baseline, 12.0+/-3.2% with terbutaline and 7.3+/-3.0% with placebo (P>0.05). Group B subjects withdrew from all beta(2) agonists for a week and MCC was remeasured. After withdrawal, baseline MCC (7.0+/-1.8%) was similar to the initial baseline value (P>0.1) and MCC with terbutaline (15.8+/-4.9%) was greater than baseline (P<0.005) but remained abnormal in most subjects. Baseline percentage predicted FEV(1) and FEF(25--75%) were 77.3+/-7.2 and 41.7+/-5.6 in group A and 59.9+/-8.1 and 29.5+/-8.4 in group B subjects, respectively. CONCLUSION: MCC was impaired in most of these asthmatics with persistent airway obstruction and sputum production, despite regular treatment with ICS and salmeterol. In addition, there was little or no stimulation of MCC acutely after terbutaline in most of these asthmatics.