The relative importance of genetic factors in determining bone mass in different parts of the skeleton is poorly understood. Lumbar spine and proximal femur bone mineral density and forearm bone mineral content were measured by photon absorptiometry in 38 monozygotic and 27 dizygotic twin pairs. Bone mineral density was significantly more highly correlated in monozygotic than in dizygotic twins for the spine and proximal femur and in the forearm of premenopausal twin pairs, which is consistent with significant genetic contributions to bone mass at all these sites. The lesser genetic contribution to proximal femur and distal forearm bone mass compared with the spine suggests that environmental factors are of greater importance in the aetiology of osteopenia of the hip and wrist. This is the first demonstration of a genetic contribution to bone mass of the spine and proximal femur in adults and confirms similar findings of the forearm. Furthermore, bivariate analysis suggested that a single gene or set of genes determines bone mass at all sites.
Hyperosmolarity of the airway surface liquid (ASL) has been proposed as the stimulus for hyperpnoea-induced asthma. We found previously that mucociliary clearance (MCC) was increased after isocapnic hyperventilation (ISH) with dry air, and we proposed that the increase related to transient hyperosmolarity of the ASL. We investigated the effect of increasing the osmolarity of the ASL on MCC, by administering an aerosol of concentrated salt solution.MCC was measured using 99m Tc-sulphur colloid, gamma camera and computer analysis in 12 asthmatic and 10 healthy subjects on three separate days, involving administration of each of the following: 1) ultrasonically nebulized 14.4% saline; 2) ultrasonically nebulized 0.9% saline; and 3) no aerosol intervention (control).The (mean±SD) volume of nebulized 14.4% saline was 2.2±1.2 mL for asthmatics and 3.2±0.7 mL for healthy subjects. This volume was delivered over a period of 5.4±1.3 and 6.4±0.7 min for asthmatic and healthy subjects, respectively. The airway response to 14.4% saline was assessed on a separate visit and the fall in forced expiratory volume in one second (FEV1) was 22±4% in the asthmatic and 3±2% in the healthy subjects. Compared to the MCC with the 0.9% saline and control, the hypertonic aerosol increased MCC in both groups. In asthmatic subjects, MCC of the whole right lung in 1 h was 68±10% with 14.4% saline vs 44±14% with 0.9% saline and 39±13% with control. In healthy subjects, MCC of the whole right lung in 1 h was 53±12% with 14.4% saline vs 41±15% with 0.9% saline and 36±13% with control.We conclude that an increase in osmolarity of the airway surface liquid increases mucociliary clearance both in asthmatic and healthy subjects. These findings are in keeping with our previous suggestion that the increase in mucociliary clearance after isotonic hyperventilation with dry air is due to a transient hyperosmolarity of the airway surface liquid. Eur Respir J., 1996, 9, 725- We have previously found that mucociliary clearance (MCC) increases immediately after hyperventilation with dry air both in asthmatic and healthy subjects [1] at the time that asthmatic subjects develop airway narrowing. Although the mechanism for this increase is unknown, we postulated that the increase in MCC after hyperventilation with dry air is due to a transient hyperosmolarity of the airway surface liquid [1]. It is possible that the increase in MCC and the bronchoconstriction that follows hyperventilation with dry air share a common mechanism.Inhalation of hypertonic saline aerosol (7%) has been shown to increase mucociliary clearance in patients with bronchitis [2] and cystic fibrosis [3] who have impaired baseline mucociliary clearance. Although, these studies suggest that hypertonic saline stimulates the mucociliary system, there are no reported studies of the effect of hypertonic saline on the MCC in asthmatic and healthy subjects with normal baseline mucociliary clearance.The aim of the present study was to investigate the effect of a hyperosmolar stimulus on MC...
It has been postulated that hypertonic saline (HS) might impair the antimicrobial effects of defensins within the airways. Alternative non‐ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance (BMC) in patients with cystic fibrosis (CF). This study reports the effect of inhalation of another osmotic agent, dry powder Mannitol (300 mg), compared with its control (empty capsules plus matched voluntary cough) and a 6% solution of HS on BMC in 12 patients with cystic fibrosis (CF). Mucus clearance was measured using a radioaerosol/gamma camera technique. Post‐intervention clearance was measured for 60 min, followed by cough clearance for 30 min. Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls. However during the post‐intervention measurement there was a significant improvement in BMC for both the mannitol (8.7±3.3%versus 2.8±0.7%) and HS (10.0±2.3%versus 3.5±0.8%). There was also a significant improvement in cough clearance with the Mannitol (9.7±2.4%) compared with its control (2.5±0.8%). Despite premedication with a bronchodilator, a small fall in forced expiratory volume in one second (FEV1) was seen immediately after administration of both the mannitol (7.3±2.5%) and HS (5.8±1.2%). Values of FEV1 returned to baseline by the end of the study. Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients. Further studies are required to establish the optimal dose and the long‐term effectiveness of mannitol. Eur Respir J 1999; 14: 678–685.
Bronchiectasis is a disease characterized by hypersecretion and retention of mucus requiring physical and pharmacologic treatment. Recently we reported that inhalation of dry powder mannitol markedly increases mucociliary clearance (MCC) in asthmatic and in healthy subjects (Daviskas, E., S. D. Anderson, J. D. Brannan, H. K. Chan, S. Eberl, and G. Bautovich. 1997. Inhalation of dry-powder mannitol increases mucociliary clearance. Eur. Respir. J. 10:2449-2454). In this study we investigated the effect of mannitol on MCC in patients with bronchiectasis. Eleven patients 40 to 62 yr of age inhaled mannitol (approximately 300 mg) from a Dinkihaler. MCC was measured over 90 min, in the supine position, on three occasions involving: mannitol or control or baseline, using a radioaerosol technique. On the control day patients reproduced the breathing maneuvers and the number of coughs induced by the mannitol. Mannitol significantly increased MCC over the 75 min from the start of the intervention compared with control and baseline in the whole right lung, central, and intermediate region. Mean (+/- SEM) clearance with mannitol was 34.0 +/- 5.0% versus 17.4 +/- 3.8% with control and 11.7 +/- 4.4% with baseline in the whole right lung (p < 0.0001). The mean number of coughs induced by mannitol was 49 +/- 11. In conclusion, inhalation of dry powder mannitol increased clearance of mucus and thus has the potential to benefit patients with bronchiectasis.
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