Thyroid function in neonates conceived after hysterosalpingography with iodinated contrast.

STUDY QUESTION: Does exposure to preconceptional hysterosalpingography (HSG) with iodinated oil-based contrast affect neonatal thyroid function as compared to iodinated water-based contrast? SUMMARY ANSWER: Preconceptional HSG with iodinated contrast did not influence the neonatal thyroid function. WHAT IS KNOWN ALREADY: HSG is a commonly applied tubal patency test during fertility work-up in which either oil- or water-based contrast is used. Oil-based contrast contains more iodine compared to water-based contrast. A previous study in an East Asian population found an increased risk of congenital hypothyroidism (CH) in neonates whose mothers were exposed to high amounts of oil-based contrast during HSG. STUDY DESIGN, SIZE, DURATION: This is a retrospective data analysis of the H2Oil study, a randomized controlled trial (RCT) comparing HSG with the use of oil- versus water-based contrast during fertility work-up. After an HSG with oil-based contrast, 214 women had an ongoing pregnancy within 6 months leading to a live birth compared to 155 women after HSG with water-based contrast. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 369 women who had a live born infant, 208 consented to be approached for future research and 138 provided informed consent to collect data on the thyroid function tests of their offspring (n = 140). Thyroid function tests of these children were retrieved from the Dutch neonatal screening program, which includes the assessment of total thyroxine (T4) in all newborns, followed by thyroid-stimulating hormone only in those with a T4 level of ≤ -0.8 SD score. Furthermore, amount of contrast medium used and time between HSG and conception were compared between the two study groups. MAIN RESULTS AND THE ROLE OF CHANCE: Data were collected from 140 neonates conceived after HSG with oil-based (n = 76) or water-based (n = 64) contrast. The median T4 concentration was 87.0 nmol/l [76.0-96.0] in the oil group and 90.0 nmol/l [78.0-106.0] in the water group (P = 0.13). None of the neonates had a positive screening result for CH.The median amount of contrast medium used was 9.0 ml [interquartile range (IQR), 6.0-11.8] in the oil-group and 10.0 ml [IQR, 7.5-14.0] in the water group (P = 0.43). No influence of the amount of contrast on the effect of contrast group on T4 concentrations was found (P-value for interaction, 0.37). LIMITATIONS, REASONS FOR CAUTION: A relatively small sample size and possible attrition at follow-up are limitations of this study. Although our results suggest that the use of iodinated contrast media for HSG is safe for the offspring, the impact of a decrease in maternal thyroid function on offspring neurodevelopment could not be excluded, as data on maternal thyroid function after HSG and during conception were lacking. WIDER IMPLICATIONS OF THE FINDINGS: As HSG with oil-based contrast does not affect thyroid function of the offspring, there is no reason to withhold this contrast to infertile women undergoing HSG. Future studies should investigate whether HSG with iodinated contrast influences the periconceptional maternal thyroid function and, consequently, offspring neurodevelopment. STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (Academic Medical Center and VU University Medical Center) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and intrepretation of the data. I.R. reports receiving travel fee from Guerbet. C.B.L. reports speakers fee from Ferring in the past and research grants from Ferring, Merck and Guerbet. K.D. reports receiving travel fee and speakers fee from Guerbet. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. V.M. reports receiving travel fee and speakers fee as well as research grants from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: Netherlands Trial Register NTR 7526 (Neonates born after the H2Oil study), NTR 3270 (original H2Oil study), www.trialregister.nl.

Treatment effect of oil-based contrast is related to experienced pain at HSG: a post-hoc analysis of the randomised H2Oil study.

STUDY QUESTION: Does pain or volume of used contrast medium impact the effectiveness of oil-based contrast during hysterosalpingography (HSG)? SUMMARY ANSWER: In women who report moderate to severe pain during HSG, the use of oil-based contrast resulted in more ongoing pregnancies compared to the use of water-based contrast, whereas in women who reported mild or no pain, no difference in ongoing pregnancies was found. WHAT IS KNOWN ALREADY: We recently showed that in infertile women undergoing HSG, the use of oil-based contrast results in more ongoing pregnancies within 6 months as compared to the use of water-based contrast. However, the underlying mechanism of this fertility-enhancing effect remains unclear. STUDY DESIGN, SIZE, DURATION: We performed a post-hoc analysis of the H2Oil study, a multicentre randomised controlled trial (RCT) evaluating the therapeutic effect of oil- and water-based contrast at HSG. Here, we evaluated the impact of pain experienced at HSG and volume of used contrast media during HSG on ongoing pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a subset of 400 participating women, pain during HSG by means of the Visual Analogue Scale (VAS) (range: 0.0-10.0 cm) was reported, while in 512 women, we registered the volume of used contrast (in millilitres). We used logistic regression analyses to assess whether pain and volume of used contrast media modified the effect of oil-based contrast on ongoing pregnancy rates. Data were analysed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: In 400 women in whom pain scores were reported, the overall median pain score was 5.0 (Interquartile range (IQR) 3.0-6.8) (oil group (n = 199) 4.8 (IQR 3.0-6.4); water group (n = 201) 5.0 (IQR 3.0-6.7); P-value 0.28). There was a significant interaction between pain (VAS ≤5 versus VAS ≥6) and the primary outcome ongoing pregnancy (P-value 0.047). In women experiencing pain (VAS ≥6), HSG with oil-based contrast resulted in better 6-month ongoing pregnancy rates compared to HSG with water-based contrast (49.4% versus 29.6%; RR 1.7; 95% CI, 1.1-2.5), while in women with a pain score ≤5, 6-month ongoing pregnancy rates were not significantly different between the use of oil- (28.8%) versus water-based contrast (29.2%) (RR 0.99; 95% CI, 0.66-1.5). In the 512 women in whom we recorded contrast, median volume was 9.0 ml (IQR 5.7-15.0) in the oil group versus 8.0 ml (IQR 5.9-13.0) in the water group, respectively (P-value 0.72). Volume of used contrast was not found to modify the effect of oil-based contrast on ongoing pregnancy (P-value for interaction 0.23). LIMITATIONS, REASONS FOR CAUTION: This was a post-hoc analysis that should be considered as hypothesis generating. The RCT was restricted to infertile ovulatory women, younger than 39 years of age and with a low risk for tubal pathology. Therefore, our results should not be generalised to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS: The underlying mechanism of the fertility-enhancing effect induced by HSG with the use of oil-based contrast remains unclear. However, these findings suggest a possible mechanistic pathway, that is increasing intrauterine pressure occurring prior to dislodging pregnancy hindering debris or mucus plugs from the proximal part of otherwise normal fallopian tubes. This information might help in the search of the underlying fertility-enhancing mechanism found by using oil-based contrast during HSG. STUDY FUNDING/COMPETING INTEREST(S): The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports consultancy for Guerbet. H.V. reports consultancy fees from Ferring. C.B.L. reports speakers' fees from Ferring and research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflict of interests. TRIAL REGISTRATION NUMBER: The H2Oil study was registered at the Netherlands Trial Registry (NTR 3270). TRIAL REGISTRATION DATE: 1 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 3 February 2012.

Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta-analysis.

OBJECTIVES: To compare, in women with infertility, the effectiveness and safety of tubal flushing using oil-based contrast medium, water-based contrast medium or their combination, and no tubal flushing, and to evaluate the effectiveness of tubal flushing on fertility outcome over time. METHODS: We performed a systematic review and network meta-analysis, searching the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, and trial registries, up to 25 September 2018. We included randomized controlled trials (RCTs) comparing the following interventions with each other or with no intervention in women with infertility: tubal flushing using water-based contrast medium, tubal flushing using oil-based contrast medium or additional tubal flushing with oil-based medium following diagnostic tubal flushing with water-based medium. The outcomes included clinical pregnancy, live birth, ongoing pregnancy, miscarriage, ectopic pregnancy and adverse events. RESULTS: Of the 283 studies identified through the search, 14 RCTs reporting on 3852 women with infertility were included. Network meta-analysis showed that tubal flushing using oil-based contrast medium was associated with higher odds of clinical pregnancy within 6 months after randomization and more subsequent live births compared with tubal flushing using water-based medium (odds ratio (OR), 1.67 (95% CI, 1.38-2.03), moderate certainty of evidence; and OR, 2.18 (95% CI, 1.30-3.65), low certainty of evidence, respectively) and compared with no intervention (OR, 2.28 (95% CI, 1.50-3.47), moderate certainty of evidence; and OR, 2.85 (95% CI, 1.41-5.74), low certainty of evidence, respectively). These results agreed with those of the pairwise meta-analysis. For clinical pregnancy within 6 months, there was insufficient evidence of a difference between tubal flushing with water-based contrast medium and no intervention (OR, 1.36 (95% CI, 0.91-2.04), low certainty of evidence). For fertility outcomes after 6 months, there was insufficient evidence of a difference in any comparison (low to very low certainty of evidence). Compared with tubal flushing using water-based contrast medium, the use of oil-based contrast medium was associated with higher odds of asymptomatic intravasation (OR, 5.06 (95% CI, 2.29-11.18), moderate certainty of evidence). CONCLUSIONS: In women with infertility undergoing fertility workup, tubal flushing using oil-based contrast medium probably increases clinical pregnancy rates within 6 months after randomization and may increase subsequent live-birth rates, compared with tubal flushing using water-based contrast medium and compared with no intervention. Evidence on fertility outcomes beyond 6 months is inadequate to draw firm conclusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Eficacia sobre el resultado de fertilidad del lavado de trompas con diferentes medios de contraste: revisión sistemática y metaanálisis en red OBJETIVOS: Comparar, en mujeres con infertilidad, la efectividad y seguridad del lavado de trompas con un medio de contraste a base de aceite, un medio de contraste a base de agua o una combinación, y el no lavado de trompas, y evaluar la efectividad del lavado de trompas en el resultado de la fertilidad con el tiempo. MÉTODOS: Se realizó una revisión sistemática y un metaanálisis en red, mediante búsquedas en las bases de datos electrónicas MEDLINE, EMBASE y el Registro Central Cochrane de Ensayos Controlados, y en otros registros de ensayos, hasta el 25 de septiembre de 2018. Se incluyeron ensayos controlados aleatorizados (ECA) que compararon las siguientes intervenciones entre sí o con la no intervención en mujeres con infertilidad: lavado de trompas con medio de contraste a base de agua, lavado de trompas con medio de contraste a base de aceite o lavado de trompas adicional con un medio a base de aceite después de un lavado de trompas con un medio a base de agua. Los resultados incluyeron el embarazo confirmado ecográficamente, el nacimiento vivo, el embarazo en curso, el aborto espontáneo, el embarazo ectópico y los eventos adversos. RESULTADOS: De los 283 estudios identificados mediante la búsqueda, se incluyeron 14 ECA que informaron sobre 3852 mujeres con infertilidad. El metaanálisis en red mostró que el lavado de trompas con medio de contraste a base de aceite se asoció con mayores probabilidades de embarazo confirmado ecográficamente dentro de los seis meses posteriores a la aleatorización y más nacimientos vivos posteriores en comparación con el lavado de trompas con medio a base de agua (razón de momios [RM], 1,67; IC 95%: 1,38-2,03), certeza moderada de evidencia; y RM, 2,18 (IC 95%: 1,30-3,65), certeza baja de evidencia, respectivamente) y en comparación con la no intervención (RM, 2,28 (IC 95%: 1,50-3,47), certeza moderada de evidencia; y RM, 2,85 (IC 95%: 1,41-5,74), certeza baja de evidencia, respectivamente). Estos resultados coincidieron con los del metaanálisis por pares. No hubo evidencia suficiente de una diferencia entre el lavado de trompas con medio de contraste a base de agua y la no intervención para el embarazo clínico dentro de los seis meses (RM, 1,36 (IC 95%: 0,91-2,04); certeza baja de evidencia). Para los resultados de fertilidad después de los seis meses, no hubo evidencia suficiente de diferencias en cualquier comparación (certeza de evidencia baja a muy baja). En comparación con el lavado de trompas con un medio de contraste a base de agua, el uso de un medio de contraste a base de aceite se asoció con mayores probabilidades de intravasación asintomática (RM, 5,06 (IC 95%: 2,29-11,18), certeza moderada de evidencia). CONCLUSIONES: En las mujeres con infertilidad que se someten a un examen de fertilidad, el lavado de trompas con medio de contraste a base de aceite aumenta la probabilidad de las tasas de embarazo clínico dentro de los 6 meses posteriores a la aleatorización y puede aumentar las tasas posteriores de nacimientos vivos, en comparación con el lavado de trompas con medio de contraste a base de agua y en comparación con la no intervención. La evidencia sobre los resultados de fertilidad después de los seis meses es inadecuada para establecer conclusiones firmes. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Immobilization or mobilization after IUI: an RCT.

STUDY QUESTION: Does 15 min of immobilization after IUI improve pregnancy rates? SUMMARY ANSWER: Immobilization for 15 min after IUI does not improve pregnancy rates. WHAT IS KNOWN ALREADY: Prior RCTs report a beneficial effect of supine immobilization for 15 min following IUI compared to immediate mobilization, however, these studies can be criticized. Given the importance for the logistics in daily practice and the lack of biological plausibility we planned a replication study prior to potential implementation of this procedure. STUDY DESIGN, SIZE, DURATION: A single centre RCT, based in an academic setting in the Netherlands, was performed. Participants were randomly assigned for 15 min of supine immobilization following IUI for a maximum of six cycles compared to the standard procedure of immediate mobilization following IUI. Participants and caregivers were not blinded to group assignment. An independent researcher used computer-generated tables to allocate treatments. Stratification occurred to the indication of IUI (unexplained or mild male subfertility). Revelation of allocation took place just before the insemination by the caregiver. The primary outcome was ongoing pregnancy rate per couple. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 498 couples diagnosed with unexplained or mild male subfertility and an indication for treatment with IUI were approached and randomized in the study, of which 244 participants were assigned to 15 min of supine immobilization and 254 participants to immediate mobilization. MAIN RESULTS AND THE ROLE OF CHANCE: Participant characteristics were comparable between the groups, and 236 participants were analysed in the immobilization group, versus 245 in the mobilization group. The ongoing pregnancy rate per couple was not found to be superior in the immobilization group (one-sided P-value = 0.97) with 76/236 ongoing pregnancies (32.2%) being accomplished in the immobilization and 98/245 ongoing pregnancies (40.0%) in the immediate mobilization group (relative risk 0.81; 95% CI [0.63, 1.02], risk difference: -7.8%, 95% CI [-16.4%, 0.8%]). No difference was found in miscarriage rate, multiple gestation rate, live birth rate and time to pregnancy between the groups. LIMITATIONS, REASONS FOR CAUTION: Owing to discontinuation of the planned treatment not all participants reached six IUI cycles or an ongoing pregnancy. However, this is as expected in IUI treatment and mirrors clinical practice. These participants were equally distributed across the two groups. Women with tubal pathology and endocrine disorders were excluded for this trial, and this might narrow generalizability. WIDER IMPLICATIONS OF THE FINDINGS: This study shows no positive effect of 15 min of immobilization following IUI on pregnancy rates. Based on available evidence today, including our study, a possible beneficial effect of supine immobilization after IUI is at least doubtful and straightforward implementation does not seem to be justified. STUDY FUNDING/COMPETING INTEREST(S): No funding was received. All authors have nothing to disclose. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR 2418. TRIAL REGISTRATION DATE: 20 July 2010. DATE OF FIRST PATIENT's ENROLMENT: 11 August 2010.

Sedentary behaviour and bone health in children, adolescents and young adults: a systematic review-supplementary presentation.

BACKGROUND: Sedentary behaviour (SB) is a potential risk factor for suboptimal bone deposition in youth. RESULTS: Total SB was negatively associated with lower extremity bone outcomes, while no association was observed with total body bone outcomes. Insufficient evidence was found for an association between total SB and lumbar spine bone outcomes. CONCLUSION: This review highlights the heterogeneity of the available evidence and emphasizes the need for well-designed studies.

Sedentary behaviour and bone health in children, adolescents and young adults: a systematic review.

Sedentary behaviour (SB) is increasing in Western societies and some studies suggest a deleterious effect of SB on bone. The aim of this systematic review was to examine the association between SB and bone health in children, adolescents and young adults. Electronic databases (PubMed, MEDLINE, PsycINFO and Science Citation Index) were searched for relevant articles up to January 9, 2017. Studies were included when results on bone health (e.g. strength, mass and structure) and either subjectively (questionnaires) or objectively (accelerometry) measured SB were reported in healthy participants ≤24 years. Two reviewers independently screened titles and abstracts for eligibility, rated methodological quality and extracted data. Seventeen observational studies were included. Several studies that used DXA or quantitative ultrasound suggested that objectively measured SB was negatively associated with lower extremity bone outcomes, such as femoral neck bone mineral density. The magnitude of this negative association was small and independent of moderate-to-vigorous physical activity. In contrast to the lower extremities, there was insufficient evidence for an association of lumbar spine bone outcomes with objectively measured SB. In high-quality studies that used DXA, no association was observed between objectively measured SB and total body bone outcomes. In studies using questionnaires, none of these relationships were observed. Well-designed longitudinal studies, objectively measuring SB, are needed to further unravel the effect of SB, physical activity and their interaction on bone health.

Is intrapartum fever associated with ST-waveform changes of the fetal electrocardiogram? A retrospective cohort study.

OBJECTIVE: To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram. DESIGN: Retrospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(®) clinical guidelines. MAIN OUTCOME MEASURES: Number and type of ST-events. RESULTS: Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events. CONCLUSIONS: Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.

Inflammatory cells seem not to be involved in idiopathic rhinitis.

Mucosal inflammatory cellular infiltrates are correlated with nasal complaints in symptomatic allergic rhinitis. Some authors suggest inflammation of a neurogenic or immunogenic nature as an underlying disorder for idiopathic rhinitis (IR). We looked at the possible involvement of inflammatory cells in the pathogenesis of IR. Nasal biopsies were taken from sixty-five IR patients with significant nasal complaints and from twenty healthy controls with no nasal complaints. Inflammatory cells were quantified using monoclonal antibodies directed against lymphocytes, antigen-presenting cells, eosinophils, macrophages, monocytes, mast cells and other IgE-positive cells. No significant differences were found, for any cell, between IR patients and controls. We conclude that inflammatory cells do not seem to play an important role in this meticulously characterised group of IR patients.

'Intranasal toothache': case report.

OBJECTIVE: This paper describes a patient with recurrent unilateral nasal discomfort and pain due to an intranasal tooth. A short overview of the literature is provided in relation to the aetiology, symptomatology, diagnosis and treatment of intranasal teeth. CASE REPORT: A 26-year-old man was referred with a history of recurrent left-sided nasal obstruction, facial pain and discomfort, and chronic purulent rhinorrhoea. Computed tomography revealed a nasal tooth, which was likely to have been the cause of these symptoms. After transnasal surgical extraction under endoscopic guidance, the patient was relieved of his complaints (at the one-year follow up). CONCLUSION: An ectopic tooth in the nasal cavity is a rare phenomenon, and in most cases the cause of an intranasal tooth remains unclear. The treatment of an intranasal tooth entails surgical extraction even though such teeth may remain asymptomatic; several cases have illustrated the potential significant morbidity associated with their occurrence.

The pathophysiological basis of pharmacological interventions in CAVD.

Calcific aortic valve disease (CAVD) results in aortic valve stenosis and is one of the most common cardiac diseases in both Western and developing countries. The burden of this disease is expected to increase rapidly in the future, but there are still no relevant pharmacological therapies available and aortic valve replacement remains the sole definite therapy. This review presents an overview of the most common causes of CAVD, followed by current debates and trials related to the onset and progression of this disease. Several differences and similarities between the different causes of CAVD are presented. Additionally, stages of CAVD are compared with stages in atherosclerosis. Finally, future directions for research on CAVD will be discussed.

A non-traumatic, blue-purple auricle: case report.

OBJECTIVE: We report a typical case of earlobe lymphocytoma. METHOD: A case report and literature review are presented. RESULTS: A 10-year-old girl presented with a blue-coloured earlobe. A diagnosis of Lyme disease was confirmed by serological tests. Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. It is caused by the spirochete Borrelia burgdorferi sensu lato. The patient was successfully treated with antibiotics. CONCLUSION: The diagnostic process and ENT symptomatology of Lyme disease and borrelial lymphocytoma are summarised and discussed.

Intralesional triamcinolone acetonide injection in hypertrophic skin surrounding the percutaneous titanium implant of a bone-anchored hearing aid.

OBJECTIVE: We present a patient with persistent hypertrophic skin surrounding the percutaneous implant of a bone-anchored hearing aid system, successfully treated with intralesional applied corticosteroids. METHOD: Case report and review of the world literature concerning bone-anchored hearing aid implantation and intralesional applied corticosteroids for the treatment of hypertrophic scars and keloids. RESULTS: Eight weeks after revision surgery to reduce surplus skin and subcutaneous scar tissue overgrowing the abutment, skin and subcutaneous scar tissue overgrowth reoccurred. As an alternative to yet another surgical procedure, the hypertrophic skin was treated with intralesional injections of triamcinolone acetonide. Three weeks after the treatment, a satisfying result was seen, and no subsequent relapse was observed. CONCLUSION: To our knowledge, this is the first, photographically well documented case report of a patient with persistent hypertrophic skin surrounding a percutaneous bone-anchored hearing aid implant, successfully treated with intralesional applied corticosteroids.

Idiopathic rhinitis, the ongoing quest.

The term rhinitis in daily practice is used for nasal dysfunction causing symptoms-like nasal itching, sneezing, rhinorrhea and or nasal blockage. Chronic rhinitis can roughly be classified into allergic, infectious or nonallergic/noninfectious. When allergy, mechanical obstruction and infections have been excluded as the cause of rhinitis, a number of poorly defined nasal conditions of partly unknown aetiology and pathophysiology remain. The differential diagnosis of nonallergic noninfectious rhinitis is extensive. Although the percentage of patients with nonallergic noninfectious rhinitis with a known cause has increased the last decades, still about 50% of the patients with nonallergic noninfectious rhinitis has to be classified as suffering from idiopathic rhinitis (IR), or rather e causa ignota. Specific immunological, clinical and sometimes radiological and functional tests are required to distinguish known causes. Research to the underlying pathophysiology of IR has moved from autonomic neural dysbalans to inflammatory disorders (local allergy), the nonadrenergic noncholinergic (NANC) sensory peptidergic neural system and central neural hyperaesthesia, still without solid ground or proof. This review summarizes the currently known causes for nonallergic noninfectious rhinitis and possible treatments. Also possible pathophysiological mechanisms of IR are discussed.

Intranasal capsaicin is efficacious in non-allergic, non-infectious perennial rhinitis. A placebo-controlled study.

BACKGROUND: Several authors described capsaicin, the pungent substance in red pepper, as an efficacious therapy for non-allergic non-infectious perennial rhinitis (NANIPER). Repeated capsaicin application induces peptide depletion and specific degeneration of the unmyelinated sensory C-fibres in the nasal mucosa. METHODS: We performed a placebo-controlled (NaCl 0.9%) study with 25 NANIPER patients. Daily record charts and visual analogue scales (VAS) were used for clinical evaluation. Nasal lavages were obtained before, during, and after treatment. RESULTS: There was a significant and long-term reduction in the VAS scores in the capsaicin group. No significant difference was found between the placebo and capsaicin treated groups for the mean group concentrations of leukotriene (LT) C4/D4/E4, prostaglandin D2 (PGD2), and tryptase. The levels of mast cell mediators, tryptase and PGD2, and leukotrienes, mediators derived from a variety of inflammatory cells, were low at baseline and comparable with levels observed in nasal lavages obtained from normals. CONCLUSION: As involvement of inflammation could not be demonstrated, it is not surprising that capsaicin has no effect on inflammatory mediators. This suggests that inflammatory cells do not play a major part in the pathogenesis of NANIPER.

The long-term effects of capsaicin aqueous spray on the nasal mucosa.

BACKGROUND: Capsaicin has been shown previously to reduce nasal complaints in patients with a non-allergic non-infectious perennial rhinitis. Proposed pathophysiological mechanisms for non-allergic non-infectious perennial rhinitis include a chronic inflammatory disorder of an antigenic or neurogenic nature as well as the possibility of a functional neuronal disorder. We hypothesized that the beneficial effect of capsaicin might be the result of a down-regulation of inflammation (by a reduction of inflammatory cells) or through modulation of neural tissue density. METHODS: Patients were treated with either a placebo or capsaicin spray solution delivering 0.15 mg of capsaicin per nostril once every second or third day for a total of seven treatments. Both sides were treated each visit. Biopsies were taken before and 2 weeks, 3 months and 9 months after the treatment period. Immunohistochemical staining of the biopsy specimen was performed to ascertain the effect of treatment on immunocompetent cell densities (quantitative) and neural tissue densities (semi-quantitative) in the nasal mucosa. RESULTS: Nasal complaints were significantly reduced in the capsaicin-treated group. The number of CD1+, CD25+, CD3+, CD68+, BMK13+, IgE+, tryptase+, and chymase+ cells did not significantly differ between capsaicin and placebo group. No significant differences between both groups were found in pan-neurogenic staining of nasal mucosa using neurofilament and synaptophysine. CONCLUSION: Capsaicin aqueous nasal spray has previously been shown to reduce nasal complaints without affecting cellular homeostasis or overall neurogenic staining up to 9 months after treatment. Immunocompetent cells are not involved in non-allergic non-infectious perennial rhinitis.

Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study.

BACKGROUND: In a recent study, we showed that intranasal capsaicin spray gives a significant and long-term reduction of symptoms in nonallergic noninfectious perennial rhinitis patients. However, in daily practice, the studied application regimen proved to be impractical because of the large number of visits required in a short period of time. In the present study, we conducted a double-blind double-dummy parallel groups trial to determine whether a more practical capsaicin application schedule is equally effective. METHODS: Thirty patients were randomized into two different treatment regimens: one group received capsaicin five times on the first day at 1-h intervals. This was followed by a placebo dummy once every second or third day for a total of five treatments 2 weeks after the capsaicin application (group A). The other group (B) received the placebo dummy five times on the first day followed by capsaicin once every second or third day for a total of five treatments 2 weeks after the placebo application. RESULTS: The visual analogue scale scores for overall nasal symptoms, rhinorrhea and nasal blockage showed significant decrease after the start of treatment in both groups, with a significantly steeper decrease in group A. A significant reduction in cold dry air dose responsiveness was also found up to 9 months after therapy in both groups, reflecting a decrease in nasal hyperreactivity. No significant changes in safety data (smell, blood pressure, heart rate) were found. CONCLUSIONS: We conclude that intranasal capsaicin seems safe to use and that five treatments of capsaicin on a single day is at least as effective as five treatments of capsaicin in 2 weeks.