Kenneth Holmberg

Prevalence of nasal polyps in adults: the Skövde population-based study.

Patients with nasal polyps present repeatedly in otorhinolaryngology practices, but the prevalence of nasal polyps in the general population is not known. Our objective was to investigate the prevalence of nasal polyps in an adult Swedish population in relation to age, gender, asthma, and aspirin intolerance. A random sample of 1,900 inhabitants over the age of 20 years, stratified for age and gender, was drawn from the municipal population register in Skövde, Sweden, in December 2000. The subjects were called to clinical visits that included questions about rhinitis, asthma, and aspirin intolerance and examination by nasal endoscopy. In total, 1,387 volunteers (73% of the sample) were investigated. The sample size was adequate, with a good fit to the whole population. The prevalence of nasal polyps was 2.7% (95% confidence interval, 1.9–3.5), and polyps were more frequent in men (2.2 to 1), the elderly (5% at ≥60 years of age), and asthmatics. Subjective symptoms of aspirin intolerance were not found to correlate with polyps. Nasal polyps were more common in adults than was stated by the a priori estimate. The Skövde population-based study is considered representative for the Swedish population.

Evaluation of Methods for Endoscopic Staging of Nasal Polyposis

Endoscopy is needed for reliable evaluation of the treatment of nasal polyposis. In this study, we compared the reproducibility of various score systems for staging nasal polyposis and the inter-individual variations between investigators. The mass of the polyps was assessed by five methods, three new techniques (numbers 1, 2 and 3) and two established ones (numbers 4 and 5). These were: 1, lateral imaging?projecting the extension of the polyps by drawing on a schematic picture of the lateral wall of each nasal cavity; 2, assessment of polyp obstruction?estimating the proportion of the total nasal cavity volume occupied by polyps; 3, nasal airway patency?determining the relationship between the patient?s patent airway lumen and an imaginary maximal nasal airway lumen; 4, a score system with four steps ad modum Lildholdt et al.?determining their relationship to fixed anatomical landmarks; and 5, a score system with three steps ad modum Lund and Mackay?determining their relationship to the middle meatus. High correlations were found between the first and the second assessments by a given investigator with all five methods used to score nasal polyposis. High correlations were also shown between the various methods. When three investigators examined a given patient, there were no significant differences between the investigators using score systems 1, 3 and 4. However, with score systems 2 and 5, there was insufficient agreement between the investigators. The patient?s symptom of nasal blockage was not a good indicator of the size of the polyps, especially as regards small polyps. Two of the best methods tested (1 and 4) were selected for further clinical studies regarding evaluation of the sensitivity of score systems to detect changes in polyp size during treatment.Endoscopy is needed for reliable evaluation of the treatment of nasal polyposis. In this study, we compared the reproducibility of various score systems for staging nasal polyposis and the inter-individual variations between investigators. The mass of the polyps was assessed by five methods, three new techniques (numbers 1, 2 and 3) and two established ones (numbers 4 and 5). These were: 1, lateral imaging projecting the extension of the polyps by drawing on a schematic picture of the lateral wall of each nasal cavity; 2, assessment of polyp obstruction estimating the proportion of the total nasal cavity volume occupied by polyps; 3, nasal airway patency--determining the relationship between the patients patent airway lumen and an imaginary maximal nasal airway lumen; 4, a score system with four steps ad modum Lildholdt et al.--determining their relationship to fixed anatomical landmarks; and 5, a score system with three steps ad modum Lund and Mackay--determining their relationship to the middle meatus. High correlations were found between the first and the second assessments by a given investigator with all five methods used to score nasal polyposis. High correlations were also shown between the various methods. When three investigators examined a given patient, there were no significant differences between the investigators using score systems 1, 3 and 4. However, with score systems 2 and 5, there was insufficient agreement between the investigators. The patients symptom of nasal blockage was not a good indicator of the size of the polyps, especially as regards small polyps. Two of the best methods tested (1 and 4) were selected for further clinical studies regarding evaluation of the sensitivity of score systems to detect changes in polyp size during treatment.

Does Allergic Rhinitis Predispose to Sinusitis

The relationship between allergic rhinitis and sinusitis is reviewed with regard to seasonal as well as perennial and fungal sinusitis. There seems to be some association between allergic processes in the nose and inflammation in the sinus mucosa but the available data are, to some extent, contradictory. Thus, the causative role of allergy in sinusitis is not clear. Prospective studies to further elucidate the influence of allergic inflammation in the pathogenesis of sinusitis are highly warranted.

Effects of topical treatment with H1 and H2 antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis

Fifteen asymptomatic subjects with allergic rhinitis participated in a double‐blind, randomized, crossover, placebo‐controlled study. The subjects were pretreated intra‐nasally with a single dose of a selective H1 receptor antagonist, levocabastine, and/or selective H2 receptor antagonist, ranitidine, prior to a nasal allergen challenge. The nasal symptoms obtained at the challenge were assessed using a scoring technique 15 min after the allergen exposure. The nasal airway resistance was determined twice prior to and once after the allergen challenge using anterior rhinomanometry. The nasal mucosal blood flow was determined before and 15 min after allergen challenge using the 133Xe wash‐out technique. After pretreatment with the H1 antagonist there was a statistically significant reduction in the number of sneezes and rhinorrhea compared to pretreatment with placebo. Pretreatment with the H2 receptor significantly decreased the rhinorrhea but not the sneeze. The nasal blockage was unaffected by both the H1 and the H2 antagonists. Pretreatment with the H1 and/or the H2 antagonists inhibited the reduction in the nasal mucosal blood flow induced by the allergen challenge to a significant degree. The present findings suggest that topical treatment with the highly selective histamine antagonist, levocabastine, inhibits allergen‐induced reflex‐mediated symptoms. H1 and H2 receptors do not appear to be involved in the regulation of the tone of the capacitance vessels. This indicates that a more complex mechanism participates in the induction of nasal blockage than the direct effect of histamine on H1 and H2 receptors on the capacitance vessels of the nasal mucosa alone. Both H1 and H2 receptors are of importance for the regulation of nasal mucosal blood flow during the allergic reaction.

Tryptase in nasal lavage fluid after local allergen challenge: Relationship to histamine levels and TAME‐esterase activity

The activation of mast cells is generally considered to be an important trigger mechanism in the immediate allergic response. This study focused on the determination of three markers of mast cell activation after an allergen challenge. Nasal allergen challenges were performed in 25 subjects with seasonal allergic rhinitis using three allergen doses increasing in 10‐fold steps in a standardised nasal lavage model for the subsequent recovery of the markers of mast cell activation. The levels of histamine and tryptase in the nasal lavage fluid were determined using radioimmunoassays, while the TAME‐esterase activity was determined using a radiochemical technique. The nasal symptoms obtained on challenge were assessed using a scoring technique. The allergen challenge resulted in significant increases in the levels of all three markers, tryptase, histamine and TAME‐esterase. In the individual measurements after the challenges there was a highly significant correlation between the TAME‐esterase levels and the tryptase levels (r = 0.71; P < 0.001), while the generation of histamine and tryptase was not significantly correlated. When comparing the cumulative generation of the three markers, significant correlations were found between all three. Allergen challenges in six non‐allergic controls using the same technique did not result in any increase in tryptase levels. The findings suggest that the determination of tryptase in nasal lavage fluid may be a valuable indicator of mast cell activation in the upper airways.

Vascular effects of topically applied bradykinin on the human nasal mucosa

To evaluate the vascular effects of topically applied bradykinin on the human nasal mucosa, 13 asymptomatic hay fever patients and 11 non-allergic subjects were challenged with diluent or bradykinin in three increasing doses. Mucosal blood flow was determined with the 133Xenon wash-out method and expiratory peak flow measurements used to assess nasal airway resistance before and after challenge. Nasal symptoms were recorded. Nasal secretion quantity was measured from preweighed paper handkerchiefs. Bradykinin induced a slight increase in nasal airway resistance which was similar in both allergic and non-allergic subjects. Nasal secretion was clearly increased after challenge with bradykinin compared with challenge with diluent in both allergic and non-allergic subjects. Bradykinin did not, however, induce any change in mucosal blood flow in either group. The present findings could be explained by direct effects of bradykinin on the vascular bed without reflex activity. Bradykinin would then induce an increase in vascular permeability with subsequent oedema formation and increased amounts of fluid on the mucosal surface. In contrast to allergen challenge, bradykinin challenge had no effect on the resistance vessels, changes of which had previously been shown to be largely reflex-mediated.

Mucosal blood flow in the human nose following local challenge with histamine

Nasal blood flow was measured using the 133Xe wash‐out method in 10 non‐allergic subjects and 13 asymptomatic hay fever patients. Determinations were made before and 15 min after challenge with diluent, 0.13 mg, 1.3 mg and 13 mg of histamine/nasal cavity. Nasal symptom scores were recorded. The nasal inspiratory peak flow was determined simultaneously in the hay fever patients. No differences in blood flow or symptom score recordings were found between the normal subjects and allergic patients under basal conditions or after histamine challenge. The nasal blood flow increased after challenge with the highest histamine dose. The increase was 34% (P< 0.05) from baseline in normals and 47% (P<0.05) in allergies. There was a dose‐dependent increase in nasal symptom scores following histamine challenge, again with no difference between normal and allergic subjects. The nasal peak flow decreased in a similar manner with a maximum decrease of 74% (P< 0.001). The present study gives further support to the notion that histamine is not the only mediator involved in vascular reactions during allergic rhinitis.

Reflex Activation in Allergen-induced Nasal Mucosal Vascular Reactions

Subjects with allergic rhinitis were challenged unilaterally with diluent and increasing doses of allergen. Challenge with the highest dose of allergen was also carried out after topical anesthesia of the nasal cavity using lidocaine. In the contralateral, unprovoked nasal cavity the mucosal blood flow was determined using the 133Xenon wash-out technique and the nasal airway resistance was determined by rhinomanometry before and after challenge. Nasal symptom scores were estimated 15 min after each challenge. Blood flow in the nasal mucosa in the unprovoked right nasal cavity decreased in a dose-dependent manner for th two highest doses of allergen where a reduction of 21% (p less than 0.05) and 26% (p less than 0.01) was obtained. Nasal airway resistance increased somewhat after the highest dose (p greater than 0.05). Topical anesthesia in the provoked nasal cavity inhibited the decrease in blood flow in the unchallenged nasal cavity. These findings suggest that the changes in the tone of the resistance vessels, but not the capacitance vessels, which are induced by allergen, are largely reflex-mediated.

Heredity of nasal polyps.

BACKGROUND Nasal polyps is a common disease but little is known about its` pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps. METHODOLOGY Patients with nasal polyps who attended the clinic were recruited to the study and were asked whether they had any close adult relatives (siblings, parents or children). We intended to recruit two relatives per patient, one of each gender, for nasal endoscopy. The prevalence of nasal polyps in these relatives was compared with the prevalence of nasal polyps in a general population. RESULTS During a 4-year period, 368 patients and 410 relatives were recruited to the study. Although we were unable to recruit two close relatives for every patient, we were able to calculate nasal polyp prevalence within families as being 19.2%. Compared with the prevalence of nasal polyps among individuals in a general Swedish population from the same geographical area, the relative risk for polyps among relatives was almost five times higher. CONCLUSION This study strongly indicates that heredity is a factor of importance for development of nasal polyps.

Relative frequencies of symptoms and risk factors among patients with chronic rhinosinusitis with nasal polyps using a case-control study

Abstract Objectives: The aim of this study was to investigate the relative frequency of important symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), the link between CRSwNP and the lower airways and the importance of smoking in CRSwNP. Method: Three hundred and sixty-eight patients with CRSwNP and 1349 controls were recruited to the study and underwent a structured interview about symptoms from the upper and lower airways, and about smoking habits. Furthermore, all participants were clinically examined using nasal endoscopy. Results: Due to interactions between the outcome variables, a multiple logistic regression model was fitted to the data. Nasal secretions, nasal blockage and impaired sense of smell were symptoms associated with CRSwNP. Furthermore, male gender, increasing age and asthma were also associated with the disease. Current smoking was less frequent among patients with CRSwNP. Conclusion: By comparing symptoms and risk factors of patients with CRSwNP with those of a large population-based control group and testing them in a multiple logistic regression model, we have been able to generate data that address key research interests in CRSwNP.