Circulating matrix metalloproteinase-9 and osteoporosis in patients with chronic obstructive pulmonary disease.

Matrix metalloproteinase-9 (MMP-9) has been implicated in airways injury in chronic obstructive pulmonary disease (COPD). Osteoporosis is common in patients with COPD, and MMP-9 is an indicator of activated osteoclasts. We hypothesized that circulating MMP-9 would be related to bone mineral density (BMD) in COPD. We explored the relationship between MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1 and -2, and BMD status in patients with COPD. A total of 70 clinically stable patients with confirmed COPD and 39 control subjects underwent spirometry, dual-energy x-ray absorptiometry to determine BMD, and venous sampling for measurement of cytokines and MMP-9 and TIMP-1 and -2. In patients, circulating MMP-9 was increased: mean (SD) 38.5 (2.2) compared with control subjects 20.1 (2.0) ng/mL, P < 0.001, whereas TIMP-1 and -2 were not different. In the patients, MMP-9 was greater in those with osteoporosis, compared with those with osteopenia, no bone disease or control subjects, and patients with osteopenia had greater MMP-9 than control subjects. The adjusted receiver operating characteristics curve area for MMP-9 detecting osteoporosis was 0.86. Patients had elevated systemic inflammatory mediators compared with control subjects, but these were unrelated to bone status. Increased circulating MMP-9 in patients with COPD was related to the presence of osteoporosis and not to lung function. MMP-9 may be a biomarker of increased bone resorption.

What community measurements can be used to predict bone disease in patients with COPD?

BACKGROUND: Osteoporosis is common in patients with COPD. Previously we have reported that loss of fat-free mass (FFM), measured by dual X-ray absorptiometry (DXA) is associated with loss of bone mineral density (BMD). In addition, in patients with a low body mass index (BMI) and a low FFM, all had evidence of bone thinning, 50% having osteopenia and 50% osteoporosis. We explored the utility of different anthropometric measures in detecting osteoporosis in a community-based COPD population. METHODS: Patients with confirmed COPD and not on long-term oral corticosteroids (n=58) performed spirometry. They underwent nutritional assessment by skinfold anthropometry, midarm circumference, calculation of both % ideal body weight (IBW) and BMI. All had DXA assessment of BMD. RESULTS: A total of 58 COPD patients had anthropometric measurements taken, with a mean age of 66.8 (SD 8.7) years, 31 (58%) were male, with a forced expiratory volume in 1s (FEV(1)) of 54.17 (20.18)% predicted. Osteoporosis was present at either the hip or lumbar region in 14 patients (24%). The useful anthropometric measurements identifying those with osteoporosis were both % IBW and BMI. The adjusted odds ratio for %IBW was 0.93 (95% confidence interval (CI) 0.87, 0.99), p=0.016 and for BMI: 0.79 (0.64-0.98), p=0.03. The receiver operating characteristics (ROC) score for both was 0.88, indicating a good fit. CONCLUSION: Osteoporosis is common, even in patients with mild airways obstruction. Nutritional assessment, incorporating a calculation of their BMI or %IBW may confer an additional benefit in detecting those at risk of osteoporosis and guide referral for BMD measurement.

Attaining a correct diagnosis of COPD in general practice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common. Diagnosis should include objective evidence of airways obstruction and spirometry is recommended in guidelines and the general medical services contract in the UK. We assessed the impact of spirometry in general practice. METHOD: We determined by questionnaire the availability, staff training, use and the interpretation results of spirometry in 72% of general practices in Wales. We reviewed the diagnosis of COPD previously made in two general practices without spirometry. RESULTS: Most practices had a spirometer (82.4%) and used it (85.6%). Confidence in use and interpretation of results varied widely: 58.1% were confident in use and 33.8% confident in interpretation. Spirometry was performed more often if confident in use and interpretation (both P<0.001) and was related to greater training periods (P<0.001). Spirometric confirmation of COPD varied widely (0-100%, median 37%). Of the 125 patients previously diagnosed with COPD 61 had spirometric confirmation, while 25 had reversible obstruction (range 210-800 mls), 34 had normal and 5 had restrictive spirometry. CONCLUSION: Despite incentives to perform spirometry in general practice, lack of adequate training in use and interpretation suggests use is confounded and the diagnosis of COPD is likely to be made on imprecise clinical grounds.

Anterior cruciate ligament reconstruction in the immature athlete: long-term results of intra-articular reconstruction.

From 1986-1992, a total of 21 ACL reconstructions were completed in 20 skeletally immature athletes with an average age of 13.7 years (range: 11.8-15.6 years). Fifteen patients underwent operative reconstruction with hamstring tendons with wide open physes and 6 patients with bone-patellar tendon-bone (BPTB). All grafts were anatomically placed through transphyseal bone tunnels in the femur and tibia. Nineteen of 20 patients (20 of 21 reconstructions) returned for follow-up at an average of 34 months (range: 17-89 months). All patients had reached skeletal maturity at follow-up. No patient had limb-length discrepancy >1 cm postoperatively. No change in tibiofemoral alignment was noted (average 4.5 versus 4.25, P=.69). Modified Lysholm score was 93/95, and 19 of 20 athletes returned to preinjury level sports activity. Ligament laxity side-to-side difference was <3 mm in 16 patients, 3-6 mm in 2 patients, and >6 mm in 2 patients. One patient developed recurrent symptomatic laxity and was lost to follow-up. Two late graft ruptures (1 hamstring and 1 BPTB graft) occurred after major reinjury during sports. In this group of patients, ACL reconstruction through bone tunnels successfully eliminated instability although the failure rate, including late graft ruptures, was higher than that usually reported for adults. No limb length or angular deformity developed as a result of the transphyseal tunnels.

Tracheal smooth muscle responses to upper airway pressure in conscious dogs.

We studied the influence of changes in pressure applied to the isolated upper airway of four conscious dogs on tracheal smooth muscle tone and breathing pattern. The dogs were prepared with a permanent side-hole tracheal stoma and were trained to sleep with a snout mask hermetically sealed in place while breathing through a cuffed endotracheal tube inserted distally into the tracheal stoma. Changes in tracheal smooth muscle tone were continuously monitored by measuring the pressure in the water-filled cuff that distended the tracheal airway while pressure changes were introduced in the upper airway independently of breathing. Increases or decreases of upper airway pressure (+/- 10 cmH2O) had little effect on tracheal airway smooth muscle tone. In contrast, an oscillating pressure wave at 30 Hz and +/- 3 cmH2O amplitude (or -3 to -7 cmH2O amplitude) caused a marked increase in tracheal airway smooth muscle tone. An elevated tracheal airway tone could be maintained over many minutes when the oscillating pressure stimulus was pulsed so that there was a cycle of 0.5 s on, 0.5 s off. This stimulus did not change the functional residual capacity but resulted in coughing, swallowing, or sighing in 54% of the tests. In the remaining tests, the pressure stimulus produced a rapid, shallow, and erratic breathing pattern. The tracheal airway constrictor response (but not the ventilatory response) was completely abolished by intravenous atropine. We suggest that upper airway vibration is a potentially powerful mechanism of reflex airway smooth muscle constriction.

Survey of young principal groups in the United Kingdom.

Of 164 young principal groups identified, 107 replied to a questionnaire asking for details of the groups and their activities. Eighty one per cent of the groups had been in existence for less than five years and 57% gave continuing medical education as one of the reasons for forming the group. The majority of groups were run informally and 55% had social meetings to which spouses were invited. The groups varied in size from six to 50 members and members' surgeries were the most popular meeting place. Clinical topics proved the most successful and group discussion was the preferred form of meeting. Groups formed for less than three years were less likely to have meetings with specialists than groups formed for three years or more and were more likely to have discussions about personal/partnership problems. Although 67% of the groups had sought outside help at some time 78% did not need any help at present.These self-help groups appear to be self-sufficient and to be meeting the continuing education and personal/social needs of young principals.