The aim of this study was to examine the association between chronic mucus hypersecretion, and FEV1 decline, and subsequent hospitalization from chronic obstructive pulmonary disease (COPD). We used data from The Copenhagen City Heart Study on 5,354 women and 4,081 men 30 to 79 yr of age with assessment of smoking habits, respiratory symptoms, and spirometry at two surveys 5 yr apart. Information on COPD hospitalization during 8 to 10 yr of subsequent follow-up was obtained from a nationwide register. Chronic mucus hypersecretion was significantly associated with FEV1 decline; the effect was most prominent among men, where chronic mucus hypersecretion at both surveys was associated with an excess FEV1 decline of 22.8 ml/yr (95% confidence interval, 8.2 to 37.4) compared with men without mucus hypersecretion, after adjusting for age, height, weight change, and smoking; in women, the excess decline was 12.6 ml/yr (0.7-24.6). Chronic mucus hypersecretion was associated with subsequent hospitalization due to COPD after adjusting for age and smoking; relative risk was 5.3 (2.9 to 9.6) among men and 5.1 (2.5 to 10.3) among women. After further adjusting for FEV1 at the second survey, the relative risk was reduced to 2.4 (1.3 to 4.5) for men and 2.6 (1.2 to 5.3) for women. Chronic mucus hypersecretion was significantly and consistently associated with both an excess FEV1 decline and an increased risk of subsequent hospitalization because of COPD.
Specific antibody synthesis in brain could be detected with maximal sensitivity by combining an advanced enzyme immunoassay with a sophisticated evaluation method that involves calculating the ratio between the cerebrospinal fluid (CSF)/serum quotients for specific antibodies (Qspec) and total IgG (QIgG). This Antibody Index (AI = Qspec/QIgG) discriminates between a blood-derived and a pathological, brain-derived specific antibody fraction in CSF and takes into account individual changes in blood/CSF barrier function. For local synthesis of polyclonal IgG in the central nervous system (QIgG greater than QLim), we propose the correction AI = Qspec/QLim (QLim represents that IgG fraction in CSF originating only from blood, calculated from the individual albumin quotient of a single patient). The normal reference range for the AI was between 0.7 and 1.3 (n = 250 control patients for each antibody species). Values of AI greater than or equal to 1.5 indicated a local specific antibody synthesis in the central nervous system. Sensitivity and precision were greatest if we analyzed the virus-specific antibodies in CSF and serum simultaneously with an enzyme immunoassay in continuous concentrations (arbitrary units) instead of titer steps. We have applied the method successfully to antibodies to measles, rubella, herpes simplex, varicella-zoster, human immunodeficiency virus (HIV), and cytomegalovirus, and to anti-Toxoplasma or -Borrelia antibodies. Clinical relevance is demonstrated for an acute zoster virus infection (monospecific response), chronic diseases such as HIV encephalitis with acute opportunistic Toxoplasma infection, and multiple sclerosis (secondary polyspecific response).
Presence of BB-specific antibodies in the cerebrospinal fluid (CSF) with evidence of their intrathecal production in conjunction with the white cell count in the CSF and typical clinical symptoms is the traditional diagnostic gold standard of Lyme neuroborreliosis (LNB). Few data are available on the CSF lactate concentration in European adults with the diagnosis of acute LNB. The objective of the study was to investigate the CSF changes during acute LNB. Routine CSF parameters [leukocyte count, protein, lactate and albumin concentrations, CSF/serum quotients of albumin (QAlb), IgG, IgA and IgM, and oligoclonal IgG bands] and the Borrelia burgdorferi (BB)-specific antibody index were retrospectively studied in relation to the clinical presentation in patients diagnosed with acute LNB. A total of 118 patients with LNB were categorized into the following groups according to their symptoms at presentation; group 1: polyradiculoneuritis (Bannwarth’s syndrome), group 2: isolated facial palsy and group 3: predominantly meningitic course of the disease. In addition to the CSF of patients with acute LNB, CSF of 19 patients with viral meningitis (VM) and 3 with neurolues (NL) were analyzed. There were 97 patients classified with definite LNB, and 21 as probable LNB. Neck stiffness and fever were reported by 15.3% of patients. Most of these patients were younger than 50 years. Polyradiculoneuritis was frequently found in patients older than 50 years. Lymphopleocytosis was found in all patients. Only 5 patients had a CSF lactate ≥3.5 mmol/l, and the mean CSF lactate level was not elevated (2.1 ± 0.6 mmol/l). The patients with definite LNB had significantly higher lactate levels than patients with probable LNB. Elevated lactate levels were accompanied by fever and headache. In the Reiber nomograms, intrathecal immunoglobulin synthesis was found for IgM in 70.2% followed by IgG in 19.5%. Isoelectric focussing detected an intrathecal IgG synthesis in 83 patients (70.3%). Elevated BB AIs in the CSF were found in 97 patients (82.2%). Patients with VM showed lower CSF protein concentration and CSF/serum quotients of albumin than LNB patients. In acute LNB, all patients had elevated cerebrospinal fluid (CSF) leukocyte counts. In contrast to infections by other bacteria, CSF lactate was lower than 3.5 mmol/l in all but 5 patients. The CSF findings did not differ between polyradiculoneuritis, facial palsy, and meningitis. The CSF in LNB patients strongly differed from CSF in VM patients with respect to protein concentration and the CSF/serum albumin quotient.
Combining the biomarker panel allows differentiating between various types of neurodegenerative dementias and contributes to a better understanding of their pathophysiological processes.
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