Prevention of relapses of nasal polyposis with intranasal triamcinolone acetonide after polyp surgery: a prospective double-blind, placebo-controlled, randomised study with a 9-month follow-up.

OBJECTIVE: To determine whether intranasal triamcinolone acetonide prevents the regrowth of nasal polyps after polyp surgery. STUDY DESIGN: Randomised, double-blind, placebo-controlled, prospective study. SETTING: Helsinki University Central Hospital. PARTICIPANTS: Sixty patients with nasal polyps entered the study. Patients were included upon arrival for elective polyp operations determined according to our standard clinical criteria. The recurrence of nasal polyposis was followed up for 9 months after surgical treatment at 3-month intervals. MAIN OUTCOME MEASURES: Anterior rhinoscopy, nasal endoscopy, olfactory threshold measurement, active anterior rhinomanometry and acoustic rhinometry were performed at every follow-up visit. RESULTS: On the whole, there was a significant inter-group difference in the change in polyp size of acetylsalicylic acid (ASA)-tolerant patients during the follow-up. In patients with acetylsalicylic acid intolerance, there was no inter-group difference (P = 0.28). No significant differences were noted for nasal resistance, nasal cavity volume, sense of smell and nasal symptoms. CONCLUSION: Triamcinolone acetonide prevents regrowth of nasal polyps after polyp surgery in acetylsalicylic acid-tolerant patients, but not in acetylsalicylic acid-intolerant patients.

Incidence of Wegener's granulomatosis in Finland 1981-2000.

OBJECTIVE: To determine the incidence and clinical presentation of Wegener's granulomatosis (WG) in Finland during the 20-year period 1981-2000. METHODS: We performed a study with retrospective data retrieval using the hospital discharge register in Finland. All available hospital case reports were reviewed. We included those patients diagnosed with and treated for WG. Demographic and clinical data at diagnosis were recorded. RESULTS: Of the 492 patients diagnosed with WG, 49% were male. Mean age at diagnosis was 53.2 years (SD 18.1). The highest rate of incidence occurred in men and women aged 65-74 years. The annual incidence per million of the population increased from 1.9 (95% CI 1.4 to 2.6) during 1981-1985 to 9.3 (95% CI 8.1 to 10.6) during 1996-2000 with gender age-adjusted incidence rate ratio 4.5 (CI 3.6 to 5.7). Only minor changes in the signs and symptoms at diagnosis occurred during the 20-year span. In 83% of cases, the ACR criteria (>or=2 criteria) were fulfilled. The mean age at diagnosis rose from 45.8 to 55.0 years and the median diagnostic delay decreased from 17 to 4 months during the two decades. CONCLUSION: The incidence of WG has increased during the last two decades with little change in clinical symptoms at presentation. At the same time, the mean age of the patients has increased and the diagnostic delay has considerably shortened.

Wegener's granulomatosis in Finland in 1981-2000: clinical presentation and diagnostic delay.

OBJECTIVE: To determine the features of clinical presentation and the diagnostic delay of Wegener's granulomatosis (WG) in Finland in 1981-2000. METHODS: A retrospective cohort study using hospital discharge registers with review of hospital case reports. We determined the spectrum of WG symptoms in relation to individual organ groups and ELK (Ear, nose, throat, Lung, Kidney) score within the first 6 months from disease onset. Diagnostic delay and contributing factors were analysed. RESULTS: Of 513 WG patients treated at Finnish specialized medical care hospitals, 489 patients had sufficient information in the first 6 months of their disease. The ENT (Ear, Nose, and Throat) system was involved in 63%; the pulmonary system in 59%, and 60% had general symptoms. Over time, the general symptoms became more common at presentation. The diagnostic delay had decreased from 17 to 4 months. CONCLUSIONS: The initial symptoms of WG remained essentially unchanged. The proportion of general symptoms increased. A considerable shortening of diagnostic delay occurred, mostly between the 5-year periods of 1981-1985 and 1986-1990, when anti-neutrophil cytoplasmic antibody (ANCA) tests were brought into routine use. ELK scores of 2 and 3 and the presence of pulmonary and general symptoms predicted a shorter diagnostic delay.

Immunoglobulins and complement factor C4 in adult rhinosinusitis.

We assessed whether complement and its factor C4 or abnormal immunoglobulin levels are associated with chronic or recurrent rhinosinusitis. We used multiple patient and control groups to obtain clinically meaningful data. Adult chronic or recurrent rhinosinusitis and acute purulent rhinosinusitis patients were compared with unselected adults and controls without previous rhinosinusitis. Associated clinical factors were reviewed. Levels of immunoglobulins, plasma C3, C4 and classical pathway haemolytic activity were analysed. C4 immunophenotyping was used to detect C4A and C4B deficiencies as null alleles. Complement was up-regulated in rhinosinusitis. C4A nulls and low IgA, IgG, IgG1, IgG2, IgG3 and IgG4 levels were all more common in chronic or recurrent rhinosinusitis patients than in unselected and healthy controls. We searched for relevant differences between the patient groups. According to stepwise logistic regression analysis, nasal polyposis [odds ratio (OR) 10.64, 95% confidence interval (CI) 2.5-45.7, P = 0.001], bronchial asthma (OR 8.87, 95% CI 2.3-34.9, P = 0.002), C4A null alleles (OR 5.84, 95% CI 1.4-24.9, P = 0.017) and low levels of IgG4 together with either IgG1 or IgG2 (OR 15.25, 95% CI 1.4-166.8, P = 0.026) were more common in chronic or recurrent rhinosinusitis than in acute rhinosinusitis patients. Isolated low IgG subclasses had limited value in patient assessment. C4A null alleles are associated with chronic or recurrent rhinosinusitis, potentially through their effect on immune defence and inflammation control. Multiple clinical and immunological parameters may need to be evaluated when searching for prognostic variables.

Does the triad of fungi, bacteria and exposure to moisture have an impact on chronic hyperplastic sinusitis?

UNLABELLED: Here we evaluated a possible relationship between chronic hyperplastic sinusitis (CHS) and moisture exposure and secondly a seasonal variation of fungal and bacterial findings in the healthy nose. In 28 CHS patients sinus mucus was collected during endoscopic sinus surgery. Samples from the nasal cavities of 19 healthy volunteers were collected by nasal lavage (NAL) in January and in September. Bacterial culture and fungal staining and culture were carried out. Histological samples from the sinus mucosa were obtained. Patients' medical history and environmental factors were enquired. Mold odor or moisture problems in the home or work environment were reported by 46% of the CHS patients. Patients who reported moisture exposure did not differ significantly from those who had not been exposed with regards to microbiological findings, tissue eosinophilia, and earlier operations. Cladosporium (16%) and Alternaria (11%) were found in NAL fluid collected in the autumn from the control subjects. No fungi were isolated from samples taken during the winter. An association between CHS or fungal sinusitis and moisture damage was not apparent in the present study. The fungal findings in the nasal cavity reflect the environmental exposure. This should be taken into account when NAL is used for microbiological studies. PRACTICAL IMPLICATIONS: Living in a moldy house or working in a similar environment may increase the risk of respiratory symptoms and infections. However, our results suggest that chronic hyperplastic sinusitis and fungal sinusitis are not associated with moisture exposure. The nose is a good collector of particles in the air. Especially samples taken by the nasal lavage method reflect the environmental exposure. This should be taken into account when this method is used for microbiological studies.

The effect of esophageal pressure monitoring on nasal airway resistance.

OBJECTIVE: Artificial obstruction of nasal airflow has been shown to increase the amount of apneas and arousals. An esophageal catheter inserted through the nasal cavity is used in sleep studies to show intrathoracic pressure variations as sign of obstructive apneas and increased respiratory resistance. This study evaluates the effect of transnasal esophageal catheter on nasal airflow. STUDY DESIGN AND SETTING: Fifty patients with problem snoring referred to our ENT clinic underwent overnight limited sleep study with an esophageal catheter. Nasal airway resistance was measured the following morning with active anterior rhinomanometry. After exclusion of 17 measurements, the results of 33 patients were compared with same parameters obtained earlier without nasal manipulation. RESULTS AND CONCLUSION: The ipsilateral nasal resistance was clearly elevated when measured with a catheter used overnight compared with the control measurement (P < 0.05). However, the combined nasal resistance was not significantly increased in this material with patent nasal airways. In patients with already compromised nasal airflow, the possibility of clinically relevant changes in nasal airflow during catheter use should be taken in account.

Breast cancer metastasis presenting as ethmoiditis.

Metastasis from primary tumours to the paranasal sinuses is infrequent. We report an unusual case of breast cancer metastasis presenting as ethmoiditis in MRI. MRI changes are unspecific and sometimes inflammatory lesions can not be distinguished from neoplastic lesions. Inflammatory changes in the paranasal sinuses are also frequently noted on MRI even in normal persons without disease. A high index of metastasis suspicion in any patient with breast cancer must be kept in mind.

Inflammatory cell and epithelial characteristics of perennial allergic and nonallergic rhinitis with a symptom history of 1 to 3 years' duration.

BACKGROUND: Perennial rhinitis is an inflammatory condition of the mucosal lining of the nose that may be caused by allergic and nonallergic mechanisms. OBJECTIVE: We sought to characterize the cellular pattern and structural changes in the nasal mucous membrane of patients with perennial rhinitis and compare them with those of control subjects. METHODS: Biopsy specimens were obtained from 27 patients with perennial allergic rhinitis (PAR), from 12 patients with perennial nonallergic rhinitis (PNAR) with eosinophils present in the nasal smear, and from 6 control subjects without rhinitis. In 10 of 27 patients with PAR who were also allergic to pollen, biopsy specimens were taken within the respective season (PARseason). In the other 17 patients, the biopsy was taken outside the pollen season (PARoutside season). Inflammatory cells were identified by using mAbs to their unique granular proteins. RESULTS: The characteristic feature of perennial rhinitis was the accumulation of activated (degranulated) mast cells and eosinophils in the nasal mucosa. The tissue eosinophil/neutrophil ratio was higher, and the loss of epithelial integrity was greater in all patient groups compared with the control subjects. The extent of epithelial damage was significantly larger in patients in the PARseason group compared with that in the PARoutside season and PNAR groups, which did not significantly differ from each other in this respect. The number of eosinophils and mast cells was higher in the PNAR group compared with the PAR groups. In all patient groups, the number of eosinophils correlated with the loss of epithelial integrity. The number of mast cells did not correlate with the extent of epithelial damage nor did the number of neutrophils, except in patients in the PARseason group. CONCLUSION: The accumulation of eosinophils and mast cells, as well as loss of epithelial integrity, was characteristic for perennial rhinitis. Loss of epithelial integrity in the nasal mucosa may be a consequence of the activity of accumulated eosinophils.

Cystic fibrosis gene mutations deltaF508 and 394delTT in patients with chronic sinusitis in Finland.

Previous studies have shown that cystic fibrosis (CF) gene mutations are linked to several severe chronic infections. Chronic sinusitis is one condition that may well be influenced by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We studied two prevalent CF mutations (AF508 and 394delTT) in a population with a low incidence of CF. The carrier frequency of the CF mutations in the Finnish population is approximately 1 in 80. We examined DNA specimens from 127 chronic sinusitis patients and found one patient who was heterozygous for 394delTT gene mutation. None of the DNA specimens had any AF508 mutation. This study shows that in a population with a low incidence of CF there was no abnormal carrier distribution of the two most common CF gene mutations in a group of chronic sinusitis patients. Routine screening of sinusitis patients for CF mutations provides no additional information on the etiology of chronic sinusitis.

Panfungal PCR and multiplex liquid hybridization for detection of fungi in tissue specimens.

A procedure based on panfungal PCR and multiplex liquid hybridization was developed for the detection of fungi in tissue specimens. The PCR amplified the fungal internal transcribed spacer (ITS) region (ITS1-5.8S rRNA-ITS2). After capture with specific probes, eight common fungal pathogens (Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Candida krusei, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Cryptococcus neoformans) were identified according to the size of the amplification product on an automated sequencer. The nonhybridized products were identified by sequencing. The performance of the procedure was examined with 12 deep-tissue specimens and 8 polypous tissue biopsies from the paranasal sinuses. A detection level of 0.1 to 1 pg of purified DNA (2 to 20 CFU) was achieved. Of the 20 specimens, PCR was positive for 19 (95%), of which 10 (53%) were hybridization positive. In comparison, 12 (60%) of the specimens were positive by direct microscopy, but only 7 (35%) of the specimens showed fungal growth. Sequencing of the nonhybridized amplification products identified an infecting agent in six specimens, and three specimens yielded only sequences of unknown fungal origin. The procedure provides a rapid (within 2 days) detection of common fungal pathogens in tissue specimens, and it is highly versatile for the identification of other fungal pathogens.

Postoperative infection following nasal septoplasty.

This retrospective study evaluates the incidence and spectrum of infectious complications in 100 consecutive adult nasal septoplasty patients. A total of 12 patients (mean age 40 years; age range 24-55 years) suffered from postoperative infection, and 3/12 had received prophylactic antibiotics. Patients presented with abscess formation (n = 7), submucosal swelling and flush (n = 4) and haematoma and high fever (n = 1). None of the patients had life-threatening complications, such as meningitis, endocarditis or septic/toxic shock. After surgical drainage, antibiotic treatment was given orally or intravenously. The mean hospitalization time was 3.6 days. To assess the clinical outcome, 8/12 patients were re-examined about 1.8 years after the operation. They all had an improved rhinological status. Septoplasty had been successful in relieving nasal obstruction in seven (88%) patients. Staphylococcus aureus was isolated from the nasal mucosa in three (38%) patients, which is in line with previous findings in healthy nasal septoplasty patients. The use of antimicrobial prophylaxis in septal surgery will be discussed.

Vascular endothelial growth factor-C and its receptor VEGFR-3 in the nasal mucosa and in nasopharyngeal tumors.

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. Both blood and lymphatic vessels of the upper respiratory tract play important roles in pathological conditions, such as infections and tumors. Here we have studied the expression of VEGF-C and its receptor VEGFR-3 in the upper respiratory system by Northern blot analysis and immunohistochemistry of human tissues, and in situ mRNA hybridization of developing mouse embryos and beta-galactosidase staining of mouse embryos having a LacZ marker gene in the VEGFR-3 gene locus. The results demonstrate expression of VEGF-C and VEGFR-3 in the developing and adult nasal respiratory epithelium and in the nasal vascular plexus, respectively. Unlike in most other tissues, in the nasal mucosa VEGFR-3 is expressed in both blood and lymphatic vessels. Expression of VEGF-C was also detected in nasal and nasopharyngeal tumor islands, which were surrounded by VEGFR-3-positive angiogenic blood vessels. These results suggest that VEGF-C and VEGFR-3 have a role in the development of the nasal submucosal vascular plexus and in its normal function and that they are associated with angiogenesis in nasal and nasopharyngeal tumors.

Unilateral blindness in a child with acute sinusitis.

Orbital infection in association with sinusitis is an emergency. It may cause visual disturbances, and in rare cases even permanent blindness by affecting the optic nerve. We report an unusual case of acute sinusitis that was complicated by irreversible visual loss in a young patient. As there is increasing evidence that respiratory viruses play an important role in the pathogenesis of acute community acquired sinusitis and spontaneous healing with only symptomatic treatment is common, the use of antibiotics in the treatment of acute sinusitis may not be needed in all cases. If the general policy to use antibiotics in acute sinusitis will be changed to more restrained and expectant, we have to be even more aware of these nowadays rare complications.

Nasal histamine reactivity; relationships to skin-test responses, allergen provocation and symptom severity in patients with long-continuing allergic rhinitis.

It has been reported that skin-test reactivity and rhinitis symptom severity weaken in the course of time. A corresponding weakening might also be seen in non-specific nasal hyper-reactivity, but the relationships of these responses are poorly understood. Our aim was to measure nasal responsiveness to histamine in a series of patients with long-continuing allergic rhinitis and to compare these measurements with skin test responses, allergen provocation and changes in severity of allergic rhinitis symptoms. A total of 73 patients in whom allergic rhinitis had been verified over 20 years earlier were re-interviewed and re-investigated. Skin prick tests with common allergens were performed and the presence of nasal allergy was confirmed by allergen provocation. Non-specific nasal hyper-reactivity was determined with nasal histamine challenge using four concentrations of histamine phosphate. The response was registered by counting sneezes, recording changes in nasal discharge and mucosal swelling and measuring nasal airway resistance. Sneezing and discharge scores showed that milder non-specific nasal hyper-reactivity was associated with lack of reactivity in skin prick tests and nasal allergen challenge. No association was observed between allergy test results and changes in nasal airway resistance during the histamine provocation. In most patients the symptoms of rhinitis had become milder or disappeared during the follow-up, but the results of the histamine challenge showed no relationship with the changes in symptom severity. In patients with allergic rhinitis, reactivity to histamine is associated with a concomitant change in skin and nasal mucosal reactivity to allergens.

Changes in skin and nasal sensitivity to allergens and the course of rhinitis; a long-term follow-up study.

BACKGROUND: Allergic skin test reactivity tends to decrease with aging, but whether the decrease is associated with changes in symptom severity and duration of the disease or determined only by aging, is poorly understood. OBJECTIVE: Our aim was to analyze skin test sensitivity some 20 years after primary testing and to relate possible changes in reactivity to aging, duration of rhinitis, and changes in severity of rhinitis symptoms. METHODS: One hundred and seven rhinitis patients who had been investigated earlier were re-interviewed and their current allergy re-assessed after a follow-up of 23 years. All patients were skin prick tested with 22 to 26 common allergens. The allergic rhinitis status was verified with nasal allergen challenge. RESULTS: Skin test reactivity showed a significant trend decreasing towards older age groups over the period between the two investigations. Rhinitis symptoms tended, on average, to become milder during the follow-up, but an association between skin test reactivity and changes in symptom severity could not be verified. CONCLUSIONS: Rhinitis symptoms tend to become milder and the allergic skin reactivity usually decreases in the long run, but these changes may occur independently of each other. In this study, the change in rhinitis symptom severity seems not to be related to the decrease in skin test reactivity.

Sense of smell in allergic and nonallergic rhinitis.

Hyposmia is a fairly common complaint in patients with long-continuing allergic or nonallergic rhinitis. Other factors such as aging, smoking, or nasal surgery may affect olfaction, but these have been little studied in rhinitis-related hyposmia. The purpose of this study was to measure and compare olfactory thresholds in 105 rhinitis patients and 104 healthy controls and to analyze possible relationships between the sense of smell and rhinitis, age, sex, smoking, prick-test results, nasal resistance, and history of nasal or paranasal surgery. The olfactory threshold was assessed with a commercially available kit of squeeze-bottle pairs. The most important variables associated with the sense of smell were determined with stepwise multiple regression analysis, and intergroup differences were assessed with analysis of variance. The reference interval of olfactory thresholds by age was estimated with regression analysis. Nasal resistance was measured by active anterior rhinomanometry. Age and rhinitis were the only variables with significant effect on the olfactory threshold in the whole series. Both the proportion of hyposmic persons and the degree of the impairment of the sense of smell were significantly higher in the rhinitis group than in the control group. The nonallergic patients' sense of smell was poorer than that of seasonal or perennial allergic rhinitis patients. A history of operations for nasal polyposis was associated with hyposmia, but operations for chronic maxillary sinusitis were not. Neither smoking habits nor sex were related to olfactory thresholds. In conclusion, hyposmia in rhinitis patients is partly attributable to age-related changes, but our results indicate that the disease itself impairs the sense of smell.

Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR.

Of 20 adults with acute community-acquired sinusitis (ACAS), rhinovirus was detected in specimens from 10 (50%) patients, including maxillary aspirates from 8 (40%) patients and nasal swabs from 9 (45%) patients, by reverse transcription-PCR (RT-PCR). Human coronavirus was detected by RT-PCR in nasal swabs from 3 of 20 patients but in no sinus secretions. These findings suggest that rhinovirus is an important cause of ACAS and that viral invasion of the sinus cavity itself may be a common event during the disease.