Cripps Aw

C-reactive protein: A critical review

&NA; We have reviewed the literature to determine the value of C‐reactive protein (CRP) measurements in the diagnosis and management of a wide range of conditions. CRP levels are of value in 6 clinical situations: (a) monitoring the response to antibiotic treatment in patients with known bacterial infections, (b) in obstetric patients with premature rupture of membranes, a rise in CRP can give early warning of intrauterine infections, (c) differentiation between active disease and infections in patients with systemic lupus and ulcerative colitis where the level of response to active disease has been previously established, (d) as a measure of disease activity and response to disease‐modifying drugs in rheumatoid arthritis, (e) early detection of complications in postoperative patients, (f) in differentiating between infection and graft‐versus‐host‐disease in bone marrow transplant patients. CRP levels have been used in an attempt to differentiate between bacterial and viral infections in various clinical situations, however the published literature does not support this role.

Ontogeny of the mucosal immune response in children.

The development of secretory IgA was followed in saliva of 263 children from birth to age 5, and in cross sectional studies of Australian school children and Papua New Guinea highland children from birth to age 5. Salivary IgA first appeared after the first week of life, peaking at 6 weeks, and falling again at 12 weeks, then rising to a peak around age 5-7, to remain at adult levels. A transient period of absent salivary IgA occurred sometime during the first 4 years in a few individuals. 5 factors were found to affect the pattern of development of IgA: the mucosal IgM response, mucosal permeability, feeding, environmental exposure, and nutritional status. The presence of IgA was associated with IgM, but not albumin, suggesting that it is secreted by plasma cells locally, rather than by transudation. On the other hand, presence of IgG in saliva was associated with that of albumin, a marker of mucosal permeability. Feeding infants formula accelerated the appearance of IgA, suggesting that this is an immune response to formula contents or to altered gut flora. In Papua New Guinea, malnourished children had lower total IgA and specific IgA antibody to E. coli and H. influenza than did normal children. The environmental stimuli of birth and entering school were both marked by dramatic increases in IgA levels. Age-matched children from Papua New Guinea had 2-3 times higher IgA levels than Australian children.

Measurement of lysozyme by an enzyme-linked immunosorbent assay.

In this study an enzyme-linked immunosorbent assay has been developed for the determination of lysozyme in saliva, serum and urine. The assay relies on the detection of specific protein rather than lytic activity, a property which has been shown to be most suitable for the quantitation of lysozyme in mucin containing substances. Our results indicate that no pretreatment is necessary for the immunochemical method. The assay is sensitive to concentrations as low as 1 microgram lysozyme/l. The intra-assay and inter-assay coefficients of variation were 5.9% and 15.8% respectively. The lysozyme level in whole saliva was 55.53 +/- 30.35 mg/l, in serum the level was 0.64 +/- 0.15 mg/l and in urine it was 0.17 +/- 0.22 mg/l. Comparisons between immunochemical determination and lytic assays showed a good correlation (serum, r = 0.79, P less than 0.01; saliva, r = 0.85, P less than 0.005; treated saliva, r = 0.96, P less than 0.001).

Seasonal variation in non-specific bronchial reactivity: a study of wheat workers with a history of wheat associated asthma.

To investigate seasonal variation in non-specific bronchial reactivity in wheat workers, we carried out histamine inhalation tests in 29 workers (28 of them men) from a small farming community with symptoms of wheat associated asthma before, during and after the 1983-4 Australian wheat harvest season. Four were cigarette smokers, and the age range was 12-54 (mean (SD) 30 (10)) years. Twenty eight subjects were atopic (one positive skinprick test result in tests with 10 common antigens), 60% reacting to house dust mite and all to at least one of eight wheat antigens. Baseline spirometry gave normal results (mean FVC1 90% (SD 8%) predicted; FVC 91% (7%) predicted). Bronchial reactivity was tested by the method of Yan et al. The cumulative doses of histamine acid phosphate (up to 3.91 mumol) that caused a fall of 20% from baseline in FEV1 was determined (PD20) and expressed as the geometric mean. In the low exposure season, May 1983, nine subjects had a PD20 (mean 1.2, range 0.3-3.9 mumol). The number rose to 19 in the summer harvest season, December 1983 (mean 0.8, range 0.07-3.9 mumol) and returned to nine in the subsequent winter, July 1984 (mean 1.8, range 0.4-3.9 mumol). The change in the number of subjects with a PD20 was significant (p less than 0.01). Four additional subjects probably had increased bronchial reactivity in the harvest season: in two the post-saline FEV1 was too unstable to give them histamine challenge and in two the challenge was inadvertently discontinued prematurely. Baseline FEV1 and FVC fell by 8% between the first and second studies (p less than 0.001); values were intermediate in the third study (FEV1 3.74, 3.44, and 3.57; FVC 4.66, 4.28, and 4.41 litres respectively). Linear modelling analysis of log PD20, season, FEV1, FVC, age, seasonality of asthma symptoms and skin test data indicated that the harvest season was the only significant determinant of variation in log PD20. It is concluded that in these wheat workers there is a seasonal variation in bronchial reactivity that may reflect a response to allergens associated with grain.

Acquired IgA deficiency

During a prospective study of the ontogeny of the mucosal immune system using saliva, one subject acquired a selective IgA deficiency at 3 years 6 months of age. Prior to this time the infant had normal ontogeny patterns for salivary immunoglobulins and the salivary IgA was confirmed to be dimeric IgA containing secretory component. Two respiratory tract infections at 3 years 4 months and 3 years 5 months were reported prior to the collection of a saliva sample which was deficient in IgA. All subsequent saliva collections remained IgA deficient. Serum and saliva collected at 11 years of age confirmed persistent IgA deficiency. There was a family history of organ‐specific autoimmune disease. The prospectively collected data indicate in this subject that the IgA deficiency was not congenital, but was acquired closely associated with two episodes of respiratory tract infections, against a genetic background of disturbed immune regulation.

Biotypes of Haemophilus parainfluenzae from the respiratory secretions in chronic bronchitis.

A total of 2401 isolates of Haemophilus parainfluenzae was isolated from respiratory secretions of 36 healthy adults and 128 patients with chronic bronchitis over a period of 1 year. The isolates were allocated to eight biotypes, by their production of indole, urease and ornithine decarboxylase. Biotypes I and II constituted most of the isolates of H. parainfluenzae from the oropharynx of controls (75%) and chronic bronchitics (c. 90%). Among the patients, there was no difference in the isolation rate between oropharyngeal swabs and sputum specimens. Biotypes III, IV, VI, VII and VIII were isolated less frequently, as was a new taxon defined here as biotype V which does not produce indole, urease or ornithine decarboxylase. Biotype III was isolated significantly less frequently from cases of chronic bronchitis than from controls, whereas biotype II was isolated somewhat more frequently from the patients, especially during acute episodes.

In vitro susceptibility patterns of nonserotypable Haemophilus influenzae from patients with chronic bronchitis

Summary The antimicrobial susceptibility patterns of 76 nonserotypable Haemophilus influenzae (biotypes I–IV) from patients with chronic bronchitis were compared against ten orally administered antimicrobial agents. In addition the sputum ampicillin concentrations one hour after standard therapy were determined in five patients with chronic bronchitis. Ampicillin resistance was demonstrated in one strain (biotype IV) which produced β‐lactamase and two strains (biotype II) with innate resistance (MIC = 4 mg/l). Resistance to trimethoprim, chloramphenicol, ciprofloxacin and cefaclor was not detected. The incidence of resistance to tetracycline was 0.5% and cephalexin 13.2%. A high incidence of resistance to erythromycin (95%) was noted. There was no association between resistance and biotype of nonserotypable H. influenzae. The sputum ampicillin concentrations from four out of five patients given standard antibiotic doses were shown to be sufficient to inhibit the growth of the majority of nonserotypable H. influenzae strains one hour after treatment. This study shows that the incidence of nonserotypable H. influenzae resistant to ampicillin is low in this community but that resistance levels to erythromycin, commonly prescribed for the management of acute bronchitis, are high. Regular sensitivity screens are important in monitoring the value of various antibiotic regimens in the management of acute bronchitis.