Olfaction in COPD.

BACKGROUND: Olfaction is poorly characterized in COPD. To test the hypothesis that olfaction is reduced in COPD, we assessed olfaction with the "Sniffin' Sticks" test and a questionnaire addressing olfaction in COPD and a corresponding control group in respect to age and sex. We also explored whether there is an association between COPD, chronic rhinosinusitis without nasal polyps (CRSsNP), and other predefined covariates with olfactory function. METHODOLOGY: Olfactory function was assessed by the score for threshold (T), discrimination (D) and identification (I), and the composite TDI score in the "Sniffin' Sticks" test and by self-reported evaluation of impaired olfaction and of "decreased sense of smell and taste" in the 22-item Sino-Nasal Outcome Test (SNOT-22) in 90 COPD patients and 93 controls. A clinical interview and ENT-examination with nasal endoscopy, skin prick test and spirometry with reversibility were performed. RESULTS: The TDI, D and I scores were significantly lower in the COPD group than in the control group. The T score was not significantly different between the two groups. Hyposmia and anosmia were present in up to 79% of patients with COPD. The prevalence of self-reported impaired olfactory function and for "decreased sense of smell and taste" - was more than two-fold greater in the COPD than in the control group. COPD, higher age, male sex and allergy were associated with a lower TDI score, while CRSsNP was not associated with the TDI score. CONCLUSIONS: COPD is associated with olfactory dysfunction and the underlying mechanisms for this dysfunction should be elucidated.

Correlation between Excessive Daytime Sleepiness (EDS) and self-reported and objective nasal characteristics.

BACKGROUND: The aim of the present study was to explore the relationship between excessive daytime sleepiness (EDS), Peak Nasal Inspiratory Flow (PNIF), and patient reported symptoms from the nose. METHOLOGY: Six hundred and fifty one consecutive patients referred to a hospital on suspicion of sleep related breathing disorder (SRBD) were included in the study. Daytime sleepiness was assessed by Epworth Sleepiness Scale (EpSS). Nasal airflow was measured with Peak Nasal Inspiratory Flow (PNIF). Symptoms of sino-nasal dysfunction and diseases were graded on Visual Analogue Scales (VAS). RESULTS: EpSS score was not correlated with nasal flow as measured by PNIF or nasal obstruction - VAS scores. There were significant associations between daytime sleepiness and patient-reported VAS-scores on nasal discharge, headache, coughing, general health and to some extent sneezing when age, gender, BMI and reported co-morbidity levels were adjusted for. CONCLUSION: A clinical implication of this is that patients with EDS may be evaluated and treated for sino-nasal disease, while medical and surgical measures to open the nose per se may not be effective therapeutic options. A scientific implication is that the relationship between SRBD and sino-nasal disease should be further investigated.

Gastro-oesophageal reflux in patients with chronic rhino-sinusitis investigated with multichannel impedance - pH monitoring.

INTRODUCTION: The pathophysiology of chronic rhinosinusitis (CRS) is unclear. It has been discussed for decades whether gastro-oesophageal reflux (GOR) may be a contributing factor for some patients. The aim of the present study was to evaluate the level of GOR in an unselected group of patients with CRS using multichannel impedance-pH monitoring. METHODS: Consecutive patients with CRS diagnosed using the EPOS2012 criteria, completed questionnaires on GOR symptoms and were offered 24-h multichannel intraluminal impedance (MII)-pH monitoring. The results were compared with a group of healthy controls. RESULTS: Forty-six patients completed MII-pH-monitoring and were compared with 45 control subjects, with comparable age and gender distributions. The median number of reflux episodes in the patients was 56.5 compared with 33 in controls, while, the numbers of proximal reflux episodes was 27.5 versus 3, respectively. Thirty nine patients had abnormal pH-impedance recordings compared with five controls. CONCLUSION: The CRS patients had significantly higher incidences of gastro-oesophageal reflux compared with asymptomatic controls. The results of this study suggest that GOR may be a causative or contributing factor of CRS.

The determining factors of peak nasal inspiratory flow and perception of nasal airflow in asthmatics.

BACKGROUND: The effect of pulmonary pathology on peak nasal inspiratory flow (PNIF) remains largely unknown. We investigated an association between a diagnosis of asthma and of lung function on PNIF when adjusted for possible confounders. Further, we investigated the perception of nasal obstruction in asthmatics compared to healthy controls when adjusted for PNIF. METHODOLOGY: Eighty-seven asthmatics and 92 non-asthmatic controls underwent PNIF (categorized into groups of high, medium and low), acoustic rhinometry (AR) and spirometry, and we assessed symptoms of nasal obstruction on visual analogue scales (VAS) in three categories. RESULTS: PNIF was significantly associated with asthma and forced expiratory volume in the first second (FEV1) (% predicted). Other factors associated with PNIF were the degree of nasal obstruction measured both subjectively on a VAS and objectively with AR, age and disease status. Asthma patients were 19 times more likely to be in a higher VAS category compared to non-asth- matic controls independent of PNIF group. CONCLUSION: Special care has to be taken when interpreting PNIF values in patients with asthma or reduced FEV1 (% predicted). The sensation of nasal obstruction in asthmatics is different from controls despite being in the same PNIF group.

Effects of an external nasal dilator strip (ENDS) compared to xylometazolin nasal spray.

Nasal blockage is a common complaint in Family Practice. Decongestive nosedrops are frequently employed therapeutic measures. Due to a considerable risk of abuse and side effects, alternatives are wanted. The purpose of this study was to elucidate to what extent ENDS might represent an alternative to decongestive nose sprays (DNS). The effects of DNS (xylometazolin) and ENDS (BreatheRight) on subjective and objective nasal blockage were compared in 89 patients. Main outcome measures were recordings of nasal symptom scores on visual analogue scales (VAS), minimal cross-sectional areas (MCA) and nasal cavity volumes (NCV) as measured by acoustic rhinometry (AR), and peak nasal inspiratory flow (PNIF). ENDS significantly increased the MCA and the NCV in the anterior 0.0-3.0 cm of the nose compared to DNS, but had no effect on MCA from 3.0 to 5.4 cm behind the nostrils. In contrast to DNS, ENDS had no effect on the posterior NCV. ENDS and DNS gave comparable increase in nasal inspiratory flow as measured by PNIF, and in the subject's own experience of nasal obstruction. ENDS may represent an alternative to DNS as a measure against nasal blockage.

Nasal symptoms and signs in children suffering from asthma.

OBJECTIVE: A link between the upper and lower airways has been convincingly demonstrated both in health and disease. To what extent the nose may be involved in children's asthma, has so far not been thoroughly investigated. In this study, we compared symptoms and signs from the upper airways in children with asthma and in children without to find out more about this. METHODS: The study group included 27 asthmatic children, the control group 29 age and sex-matched healthy volunteers. The children were investigated by a senior ENT-specialist. Their parents completed questionnaires about symptoms and signs of upper airway disorders. Skin prick tests, total IgE, acoustic rhinometry, and an X-ray of the epipharynx were performed. The data from the groups were compared. RESULTS: Nasal blockage, mouth breathing, day time sleepiness, apnoeas, itching, sneezing, and hearing impairment were more prevalent in asthmatics compared with controls (p<0.05). For nasal blockage the mean VAS-scores were 52.4 and 30.6 for asthmatics and controls, respectively. For daytime sleepiness the corresponding figures were 34.6 and 23.1. The adenoid-nasopharynx-index was larger, indicating reduced palatal airway in the former compared with the latter (p<0.05). CONCLUSIONS: As the site of upper airway obstruction in asthmatic children appears to be the epipharynx, the adenoids may play a key-role.

Effects of benzalkonium chloride on innate immunity physiology of the human nasal mucosa in vivo.

OBJECTIVE: Benzalkonium chloride (BC) is a preservative commonly used in nasal decongestant sprays. It has been suggested that BC may be harmful to the nasal mucosa. The present study, involving healthy volunteers, examines effects of BC on nasal mucosal end-organ functions. METHODS: Isotonic saline and BC (0.1 mg/mL) were administered acutely to the nasal mucosa using a nasal pool device. Nasal symptoms were determined. Nasal lavage fluid levels of alpha2-macroglobulin and fucose were measured as indices of plasma exudation and glandular secretion, respectively. In addition, BC (0.1 mg/mL) was given as single actuations of 100 microL per nasal cavity three times daily for 10 days. The ability of histamine (0.4 mg/mL) to evoke nasal symptoms and plasma exudation responses was determined before and after the repeated BC administration series. RESULTS: BC produced immediate nasal smart or pain (P < .05), but tolerance to this response developed by repeated administrations. BC increased nasal mucosal output of fucose (P < .05), whereas nasal lavage fluid levels of alpha2-macroglobulin were unaffected. Histamine produced significant symptoms and mucosal exudation of alpha2-macroglobulin (P values < .01), equally before and after the 10 days of BC exposure. CONCLUSIONS: BC in dosages commonly used as preservative in nasal decongestant sprays produced short-term glandular secretion and nasal smart or pain. However, 10 days' frequent exposure to BC was not associated with untoward symptomatic effects, nor was a sensitive mucosal variable such as histamine-induced exudative responsiveness affected by this repeated exposure 1 BC.

Benzalkonium chloride interferes with energy production, secretion and morphology in human blood platelets.

Benzalkonium chloride (BC) is a bactericidal compound used as a topical antiseptic and as a preservative in various products for local treatment, e.g., eye and nose drops. BC is toxic to human cells, including those of the respiratory mucosa. Few studies have, however, focused on what cellular functions BC interferes with. The effects of BC were studied on washed human blood platelets in vitro . Cellular energy production as well as secretion were studied. Incubation of platelets with BC resulted in rapid swelling and toxic morphological changes. After incubation with BC oxidation of [1-14C] palmitate was inhibited, and both lactate dehydrogenase and endogenous serotonin were spontaneously released. Thrombin-induced secretion of serotonin was strongly reduced after BC exposure. Histological changes with increased size, spherical form, decreased numbers of pseudopodia, loss of an intact continuous tubulus system and reduced number of granules were found by scanning and transmission electron microscopy. It is concluded that the toxic effects of BC are because of interference with membrane function and energy production.

The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride.

Fifty rats were treated with topical nasal steroids with and without the preservative benzalkonium chloride in their right nostril twice daily for 21 days, while the left nostrils were exposed to 0.9% NaCl. By cutting the noses serially in frontal sections, the structure of the mucosal lining of all parts of the nose could be investigated. Areas with squamous cell metaplasia were observed in all nostrils exposed to topical steroids containing benzalkonium chloride. Such alterations were not observed in any nasal cavities exposed to the topical nasal steroid without the preservative or to 0.9% NaCl. In conclusion, benzalkonium chloride appears to be potentially toxic to the mucosa in vivo.

[Allergic rhinitis. Epidemiology, pathogenesis, investigation and treatment]. / Allergisk rhinitt. Epidemiologi, patogenese, utredning og behandling.

The incidence of allergic rhinitis is increasing, as is our knowledge of its pathogenesis, epidemiologic factors and optimal therapeutic principles. This paper discusses various allergy promoting factors and gives a brief update on current immunological concepts of allergy. Recent achievements in the pathogenesis of allergic rhinitis are discussed, as well as pharmacological and non-pharmacological treatment.

Effects of topical nasal steroids on human respiratory mucosa and human granulocytes in vitro.

Human respiratory mucosa and human granulocytes were exposed to topical nasal steroids in vitro. The preparations containing benzalkonium chloride and benzalkonium chloride alone destroyed the mucosa within 10 days. The same preparations also inhibited human neutrophil actin polymerization, degranulation and oxidative burst in vitro in a time and concentration dependent manner. Preparations without benzalkonium chloride, as well as the steroid compounds themselves, did not have these effects. It is concluded that benzalkonium chloride has toxic effects on human respiratory mucosa and human neutrophils in vitro.

Nonadhesive stationary organ culture of human bronchial mucosa.

The supply of fresh bronchial tissue from human donors for in vitro culture is limited. Routine fiberoptic bronchoscopy offers a safe and easy procedure for obtaining minor biopsies and we wanted to see if the material provided could be used for organ culture by using a simple liquid overlay technique. Bronchial biopsies were cut into fragments 400-500 microns and kept immersed in a standard serum-supplemented medium for 40 days. An agar base prevented adhesion of the tissue. By light and electron microscopy it was shown that the tissue fragments had a differentiated epithelium at their surface throughout the culture period. An outgrowth of epithelial cells on the scaffold of the exposed stroma, covering the surface of the whole fragment, occurred within the first 5 days of culture. This epithelium was partly ciliated, 2-4 cell layers thick with squamous and cuboidal cells and expressed epithelial markers (cytokeratin and Ber-Ep4). The amount of cilia increased during the first 15 days of culture. The epithelium rested on a neosynthesized basement membrane as visualized by electron microscopy and immunohistochemistry with antibodies directed against collagen IV, laminin, and fibronectin. The central stroma consisted of loose connective tissue with fibroblasts. This simple tissue culture model combines maintenance and neoformation of bronchial epithelium on top of a living natural substrate, thus enabling direct biological studies on clinical biopsy material under perfectly viable conditions.

[Chronic non-allergic rhinitis. Etiology, diagnosis and treatment]. / Kronisk ikke-allergisk rhinitt. Arsaker, utredning og behandling.

Chronic rhinitis can be defined as an inflammation of the nasal mucosa lasting for more than three months. The condition may be due to allergy or infection, or to a number of non-allergic and non-infectious causes, such as trauma, hormonal imbalance, toxic influence or locally applied drugs. The etiology, diagnostic procedures and treatment of non-allergic chronic rhinitis are discussed.

The effect of a benzalkonium chloride-containing nasal spray on human respiratory mucosa in vitro as a function of concentration and time of action.

Human respiratory mucosa was exposed to oxymetazoline nasal spray in varying concentrations and for varying periods of time in vitro. The drug destroyed the tissue in a concentration- and time-dependent manner. In the experiments with various concentrations of the spray, some tissue fragments retained their viability throughout the experiment. This number increased parallel to a decrease in concentrations of the test substance. All the tissue fragments exposed to undiluted nose spray underwent severe destructive alterations during the exposure period. These alterations appeared first and were most extensive in those exposed for the longest periods of time. It has previously been demonstrated that the toxic effect of oxymetazoline nasal spray in vitro is probably due to the preservative benzalkonium chloride. The apparent lack of consistency between the toxic effects of benzalkonium chloride in vitro and in vivo is discussed, with special reference to protective systems absent in vitro but present in vivo.

The effect of decongestive nosedrops on human respiratory mucosa in vitro.

The aim of this study was to investigate the morphological effects of decongestive drops and sprays on human respiratory mucosa in vitro. Precultured fragments of adenoid tissue in a specially designed tissue culture system were exposed to decongestive preparations for 10 minutes once a day for 10 days. Tissue exposed to preparations preserved with benzalkonium chloride and tissue exposed to benzalkonium chloride alone underwent severe morphological alterations. Unpreserved decongestive substances did not have this effect. Benzalkonium chloride is a well-documented toxic substance in several respects. Supported by previous studies, it may seem unfortunate to use it as an additive in decongestive preparations.

Inhibition of human neutrophil actin polymerization, phagocytosis and oxidative burst by components of decongestive nosedrops.

Human neutrophil functions have been examined after exposure of leukocytes to components of decongestive nosedrops in vitro. Both the vasoactive components oxymethazoline chloride and xylomethazoline chloride, as well as the preservative benzalkonium chloride, showed a concentration- and time-dependent deleterious effect on neutrophil actin polymerization, phagocytosis and oxidative burst. The most toxic of the drug components was benzalkonium chloride, which in the commercial nosedrops tested was present in concentrations about 20 times higher than that compatible with intact neutrophil functions. These findings suggest possible inhibition of mucosal neutrophil activity following exposure to nosedrops in vivo, and support earlier reports that have questioned the use of preservatives in decongestive nosedrops.

Human respiratory mucosa in a nonadhesive stationary organ culture system.

Fragments of human adenoid tissue were transferred to a nonadhesive, stationary organ culture system. The culture period was 40 days. In culture, beating cilia could be observed at the surface of the fragments. Light microscopy, scanning electron microscopy, and transmission electron microscopy showed that the tissue fragments were covered by a multilayered, pseudostratified, ciliated epithelium. Beneath the epithelium was a basement membrane. At the start of the culture period, the central parts of the fragments were dominated by lymphocytes. These lymphocytes gradually disappeared and were replaced by a collagen-containing stroma with scattered fibroblasts. The tissue fragments can be used as an organ culture model for normal respiratory mucosa.

Ultrastructural investigation of fetal rat brain hemisphere tissue in nonadherent stationary organ culture.

Fetal rat brain fragments grown in nonadherent stationary organ culture for 50 days have been investigated ultrastructurally. Synaptogenesis and myelin formation occurred at the same time as the corresponding time-dependent events in the developing brain in vivo. Intermediate junctions were observed between cellular processes lining a central cavity in the fragments and later associated with astrocytes at the surface. Gap junctions and tight junctions were also present. In some fragments cilia were observed in the central cavity. Subependymal basement membrane labyrinths were observed in all fragments after 10 days in culture. The ultrastructural characteristics and the tissue-like structure in general were preserved for at least 50 days in this tissue culture system. The brain fragments may therefore be a valuable supplement to existing culture methods for nervous tissue.