The inflammatory biomarker YKL-40 at admission is a strong predictor of overall mortality.

OBJECTIVES: YKL-40 is an inflammatory biomarker associated with disease activity and mortality in patients with diseases characterized by inflammation and tissue remodelling. The aim of this study was to describe the prognostic value of YKL-40 in an unselected patient population. DESIGN: In consecutive patients admitted to hospital during a 1-year period, blood was collected and information regarding final diagnosis and mortality was collected. Median follow-up time was 11.5 years. SETTING: District hospital, Copenhagen, Denmark. PATIENTS: A total of 1407 patients >40 years of age were admitted acutely. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Median YKL-40 was increased in patients (157 µg L(-1) , range 13-7704 µg L(-1) ) compared to healthy controls (40 µg L(-1) , range 29-58 µg L(-1) ; P < 0.001). Patients with YKL-40 in the highest quartile had a hazard ratio (HR) of 7.1 [95% confidence interval (CI) 4.2-12.0] for all-cause mortality in the first year and 3.4 (95% CI 2.8-4.2) in the total study period, compared to those in the lowest quartile (HR = 1). The HR for death for all patients with YKL-40 above the normal age-corrected 95th percentile was 2.1 (95% CI 1.6-2.7) after 1 year and 1.5 (95% CI 1.3-1.7) during the total study period, compared to patients with YKL-40 below the age-corrected 95th percentile. The results of multivariable analysis showed that YKL-40 was an independent biomarker of mortality; this was most significant in the first year. YKL-40 was a marker of prognosis in all disease categories. The HR for death was increased in patients with YKL-40 above the normal age-corrected 95th percentile in healthy subjects independent of type of disease (all P < 0.001). CONCLUSION: The level of YKL-40 at admission is a strong predictor of overall mortality, independent of diagnosis and could be useful as a biomarker in the acute evaluation of all patients.

Intranasal corticosteroids for allergic rhinitis: superior relief?

Whether first-line pharmacological treatment of allergic rhinitis should be antihistamines or intranasal corticosteroids has been discussed for several years. First-generation antihistamines are rarely used in the treatment of allergic rhinitis, mainly because of sedative and anticholinergic adverse effects. On the basis of clinical evidence of efficacy, no second-generation antihistamine seems preferable to another. Similarly, comparisons of topical and oral antihistamines have been unable to demonstrate superior efficacy for one method of administration over the other. Current data documents no striking differences in efficacy and safety parameters between intranasal corticosteroids. When the efficacy of antihistamines and intranasal corticosteroids are compared in patients with allergic rhinitis, present data favours intranasal corticosteroids. Interestingly, data do not show antihistamines as superior for the treatment of conjunctivitis. Safety data from comparative studies in patients with allergic rhinitis do not indicate differences between antihistamines and intranasal corticosteroids. Combining antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis does not provide any additional effect to intranasal corticosteroids alone. On the basis of current data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis than antihistamines.

Kartagener's syndrome. Preliminary report on cilia structure, function, and upper airway symptoms.

Our study was designed to examine the motility and ultrastructure of cilia from the nose of patients with Kartagener's syndrome. Microphoto-oscillographic recording from single cells showed that the patients had in fact motile cilia, although the number was reduced. Asynchrony within the single cell was a more consistent feature. The first results of blind, quantitative microscopy showed the ultrastructural defects, described earlier, but the overlapping with a normal control group was considerable. Only one of nine patients had no dynein arms and completely immotile cilia; an observation which renders the term "the immotile-cilia syndrome" a misnomer. The ear-nose-throat symptoms were characterized by daily nose-blowings since birth, recurrent sinusitis, and chronic secretory otitis media. On the other hand, the frequency of acute purulent otitis media and of common colds appeared to be normal.

Effect of nasal inflammation and of intranasal anti-inflammatory treatment on bronchial asthma.

It is logical to look upon the nose and the bronchi as integrated parts of one 'united airway' and we would like to advance the hypothesis that optimal management of airway disease, caused by inhaled allergens, may necessitate control of inflammation in all parts of the airways. Nasal inflammation can aggravate asthma symptoms, and there is a rationale for giving intranasal anti-inflammatory treatment to patients with asthma. (i) Inhaled allergens are predominantly deposited in the nose, whether a patient suffers from rhinitis, asthma or both. (ii) Antigen presentation consequently takes place in the nose, and the response of the airway immune system is thus initiated in the nasal mucous membrane. (iii) Antigen presentation in the nose may possibly induce cell recruitment and activation not only in the nasal mucosa but also in the lower airways. (iv) Suppression of nasal inflammation may therefore be necessary for optimal management of asthma.

Quantitative study of goblet cells in the upper lobe of the normal human lung.

Goblet-cell density and distribution were studied in ten specimens of the human adult lung. The bronchial tree of the left upper lobe was dissected, and the bronchial mucosa separated and stained by the whole-mount periodic acid-Schiffalcian blue method. There was a significant fall in the goblet-cell density from the proximal to the distal airways. In the upper division, the number decreased from 144 cells per field (second generation) to 80 cells per field (14th generation), and in the lingular division it decreased from 137 (fourth generation) to 77 cell (18th generation). The overall goblet-cell density for the upper lobe was 113 cells per field, corresponding to 6,400 cells per square millimeter. No particular pattern in cell distribution was noticed; the cells were irregularly distributed all along the bronchial tree without any well-defined distribution pattern. In the ten lung specimens studied, goblet-cell density did not correlate with smoking habit, sex, or age.

Cold air-induced rhinorrhea and high-dose ipratropium.

A high dose of the cholinoceptor antagonist ipratropium bromide, in the form of a nasal spray, was tested on cold air- and hot soup-induced rhinorrhea in order to determine to what extent these types of rhinorrhea are reflex-mediated hypersecretions from nasal glands. Fourteen normal volunteers were examined in a placebo-controlled study. A single dose of ipratropium bromide (400 micrograms) caused a 73% reduction of cold air-induced rhinorrhea and a 66% reduction of hot soup-induced rhinorrhea. It is concluded that a major part of the nasal discharge induced by these stimuli is reflex-mediated, and consequently may be treated by a cholinoceptor antagonist, such as ipratropium.

Lymphocyte subsets in normal airway mucosa of the human nose.

The distribution and number of lymphocytes, monocytes/macrophages, and cells expressing HLA-DR antigen were studied in frozen biopsy sections of nasal mucosa from 40 healthy adults, using monoclonal antibody avidin-biotin immunoperoxidase techniques. The lymphocyte to monocyte/macrophage ratio was estimated to be 10:1; the T cell to B cell ratio was 3:1; and the T helper/inducer cell to T suppressor/cytotoxic cell ratio averaged 2.5:1. Regional differences were observed with a relatively increased number of T suppressor/cytotoxic cells around submucosal glands, and a relatively large number of B cells in lymphocyte aggregates in the lamina propria. The HLA-DR antigen was expressed in epithelial cells, suggesting involvement of surface epithelium of human airway in local immune responses.

Oral decongestant in acute otitis media. Results of a double-blind trial.

In order to investigate the influence of an orally administered decongestant, norephedrine, upon the clinical course of acute otitis media and tubal function, a double-blind trial was performed in Copenhagen in December, 1976-February, 1977, in which 93 patients, aged 6 months to 10 years, with 135 ears with acute otitis media, were treated either with norephedrine or placebo in a randomized order. Most other treatment was avoided except for pain-relieving baby aspirins. The effect of norephedrine seemed to be no other than that of placebo. Because of this inefficacy of norephedrine the authors have, therefore, a material of patients with acute otitis media where the main treatment was pain-relieving aspirin. The use and abuse of antibiotics in the treatment of this disease are discussed, and the authors stress the necessity of performing controlled studies of the efficacy of antibiotics in acute otitis media, since such studies do not exist.

Effects of corticosteroid therapy in non-allergic rhinosinusitis.

Corticosteroids have a multifactorial effect initiated by their binding to a specific cytoplasmic glucocorticoid receptor. At the cellular level there is a reduction in the number of antigen-presenting cells, in the number and activation and T cells, in the number of epithelial mast cells, and in the number and activation of eosinophils. Steroids have a proven effect on symptoms and signs in non-allergic rhinosinusitis with eosinophilia and in nasal polyposis. Topically applied drugs, studied in many controlled trials, reduce rhinitis symptoms, improved nasal breathing, reduce the size of polyps and their recurrence, but have a poor effect on the sense of smell and no direct effect on sinus pathology. Systemic steroids, less well studied, appear to have an effect on all types of symptoms and pathology, the sense of smell included. A short course of systemic steroids is as effective as polypectomy with a snare. Individualized management of nasal polyposis and non-allergic rhinosinusitis with eosinophilia may consist of long-term topical steroids, short-term systemic steroids, or surgery, in various combinations.

Immunological barriers in the nose and paranasal sinuses.

This review deals mainly with lymphocyte subsets in the human nasal mucosa, and with the common cold. Lymphocytes have recently been characterized in biopsy specimens by an immuno-histochemical method (the avidin-biotin, monoclonal antibody peroxidase technique). In summary, the overall T:B cell ratio was 3:1 and that of T helper cells to T suppressor was 2.5:1; topographical differences within the nasal mucosa were identified. Non-specific defence systems, such as interferon, provide some protection against rhinovirus infection, but most important is the presence of specific antibodies against a given antigenic type of virus. Recent results have suggested that a rhinovirus infection does not cause a marked destruction of the epithelial lining, that it is spotty in the nasal mucosa, and that it is most prominent in the nasopharynx. Increased knowledge about the site of infection and how symptoms are produced is essential for a rational approach to the development of anti-viral therapy.

Diurnal variation of nasal protein concentration.

In normal subjects a marked diurnal variation was disclosed in the concentrations of immunoglobulin G (IgG), IgA and albumin in nasal secretion, the night values being 4.5-5.5 times higher than those during the day. It is suggested that this is due to changing secretory activity of the nasal glands.

A new anti-allergic drug, ICI 74.917 aerosol.

Ten hay fever patients were challenged intranasally with allergen before, half an hour, 2 hours and 4 hours after intranasal use of disodium cromoglycate powder, placebo and ICI 74.917, a new serosoled compound with anti-allergic action. The new compound showed a maximum protective effect after half an hour, and a significant difference was found also after 2 hours, and a significant difference was found also after 2 hours. The effect was also significantly better than that of disodium cromoglycate powder. The results were positive enough to make further human studies of ICI 74.917 desirable.

Concentration of immunoglobulins in nasal secretion from children with recurrent infections in the upper airways.

Concentrations of immunoglobulin G (IgG), IgA, IgE and albumin were determined in nasal secretion from 14 children suffering from chronically recurrent infections in the upper airways and from normal subjects. The only statistically significant difference observed was increased albumin values during infection.

Primary and secondary ciliary dyskinesia.

It has recently been shown that patients with Kartagener's triad and also some subjects with similar symptoms, but without situs inversus, have a congenital abnormality of cilia as an explanation for their chronic airway symptoms; this disease has been named "the immotile-cilia syndrome" or more correctly "primary ciliary dyskinesia". Studying 27 such patients, we have found daily nose blowings since birth, chronic-recurrent sinusitis, and chronic secretory otitis media highly characteristic features. The frequency of common colds was not increased, and most patients did not suffer from repeated episodes of acute purulent otitis media. The number of ciliated cells with immotile cilia was increased, but only a single patient had completely immotile cilia; also the degree of asynchrony within the single ciliated cell was increased. Electron microscopy showed a decreased number of dynein arms in some patients, and abnormal arrangement of microtubules in others. Some patients, however, had normal ultrastructure, and this appeared to be associated with a hyperfrequent beating pattern. At least three subgroups of patients with primary ciliary dyskinesia can be delineated based on the motility-ultrastructure studies. Bacterial infection tends to reduce the number of ciliated cells with motile cilia, and viral infection (common cold) gives a very marked and long-lasting reduction in the number of ciliated cells. This may account for some otherwise unexplainable subchronic symptoms from nose and throat.

Light and scanning electron microscopy of nasal biopsy material from patients with naturally acquired common colds.

As our knowledge of the histopathology of common colds is very limited, we have undertaken a blind quantitative examination by scanning electron microscopy and light microscopy of 56 nasal biopsies, taken from 29 volunteers with naturally acquired colds. In agreement with earlier reports we found evidence of sloughing of epithelial cells, but in contrast to in vitro experiments, this did not result in a destruction of the epithelial lining, which by and large remained continuous, with structurally normal cell borders. There was a significant increase in the number of neutrophils, both in epithelium and in lamina propria, already on the 2nd day of the disease, and the hypothesis is advanced that the virus infection itself is the cause of the local neutrophilia. The only other abnormality demonstrated was an increased number of extracellular erythrocytes in the acute stage. The histological picture was not suggestive of an involvement of epithelial mast cells in the inflammation.

The nasal mucosa during long-term treatment with beclomethasone dipropionate aerosol. A light-and scanning electron microscopic study of nasal polyps.

Blind examination by light- and scanning electron miscroscope of a total of 142 biopsies from nasal polyps was carried out before and after continuous intranasal treatment with beclomethasone dipropionate aerosol, 400 microgram/day, for a period of 9-36 months. The degree of tissue oedema, the number of infiltrating eosinophil cells and the number of goblet cells in the epithelium decreased significantly. There was no change in the type of surface epithelium during treatment, and no tendency towards squamous cell metaplasia. The study suggests that beclomethasone dipropionate treatment for a period of a few years will not cause atrophic rhinitis.

Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. I. Treatment and rationale.

Beclomethasone dipropionate is a potent corticosteroid, which when applied by a pressurized metered dose aerosol in the airways has pronounced anti-allergic effects with no risk of systemic steroid side effects at the recommended dosage. An impressive effect in hay fever and perennial rhinitis has been demonstrated. A double-blind short-term trial showed that the drug was effective in about 80% of patients suffering from moderate to severe nasal polyposis. A study of the long-term effects on the nasal mucosa is indicated.

[Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. III. Morphological studies and conclusions].

Morphological studies during the treatment of patients with nasal polyps with beclomethasone dipropionate aerosol for one year showed a trend towards a decrease in the number of eosinophils in nasal smears and falls in the increased concentrations of albumin, IgG and IgE in the nasal secretion. No change in the histological picture of the polypous tissue except increased density was observed. By scanning electron microscopy, no change in the surface structure of the nasal mucous membrane was noted. As morphological studies did not reveal any sign of adverse effects, beclomethasone dipropionate may be regarded as a valuable drug in the treatment of nasal polyps. The indications for its clinical use and supplementary therapy are discussed.

Long-term treatment of nasal polyps with beclomethasone dipropionate aerosol. II. Clinical results.

The effect of a one-year treatment with intranasal beclomethasone dipropionate in 33 patients with long-standing nasal polyps was determined. About 80% of the patients obtained good or excellent relief of symptoms. No adverse reactions of any importance occurred. It is suggested that intranasal beclomethasone dipropionate is close to the ideal basic treatment for patients with nasal polyps.

Comparison between different techniques for measuring nasal patency in a group of unselected patients.

Many techniques for measuring nasal patency have been developed in search for a reliable, easily performed and reproducible method. Rhinomanometry is easily performed in the clinic but daily records of nasal blocking cannot be obtained. In this study we examined the correlation between posterior rhinomanometry (PR), nasal peak flow (nPF), the ratio nasal patency index (NPI), and the opening interrupter method (Rtn) for measuring nasal patency. Twenty-eight subjects with no symptoms of rhinitis and 20 patients with diagnosed rhinitis were investigated. A significant (p less than 0.05) correlation was found between PR and nPF after stratification according to the diagnosis of rhinitis and between nPF, PR, and height. All other correlations tested proved non-significant. We conclude that PR is the method which ought to be used in the hospital, but nPF is an easy way to measure nasal patency and might even be used by the patient at home.