RESUMO
PURPOSE: Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, is a new treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps. However, data on the effect of dupilumab on histological changes in nasal polyp tissue are lacking. We aimed to investigate the effect of dupilumab on real-life clinical conditions and nasal polyp tissues from patients with eosinophilic chronic rhinosinusitis (ECRS), which is a refractory subtype. METHODS: We conducted an open-label, prospective, observational, single-centre study on 63 patients with refractory ECRS on the basis of the criteria of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study. These patients had a history of surgery and received dupilumab for 24 weeks. Patient-reported sinonasal symptoms, T&T olfactometry and nasal polyp scores were prospectively evaluated. In 23 patients with residual nasal polyps following dupilumab treatment, changes in systemic and local periostin expression, and total collagen deposition in nasal polyp tissues were investigated before and after dupilumab administration. RESULTS: Dupilumab rapidly improved sinonasal symptoms and reduced the nasal polyp score 24 weeks after initiation. 40 (63.5%) patients had resolution of nasal polyps, but the reduction was limited in the remaining 23 (36.5%) patients. Periostin expression in serum and nasal lavage fluid was decreased, whereas periostin and the total collagen deposition area in subepithelial tissues in residual nasal polyps were enhanced after dupilumab administration. CONCLUSION: Dupilumab improves sinonasal symptoms and reduces the nasal polyp score in refractory ECRS. Periostin-associated tissue fibrosis may be involved in the differential effect of dupilumab on nasal polyp reduction.
Assuntos
Anticorpos Monoclonais Humanizados , Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/metabolismo , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Periostina , Estudos Prospectivos , Sinusite/complicações , Fibrose , Colágeno , Doença CrônicaRESUMO
BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA. CASE PRESENTATION: We report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy. CONCLUSION: To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Asma , Síndrome de Churg-Strauss , Eosinofilia , Granulomatose com Poliangiite , Feminino , Humanos , Pessoa de Meia-Idade , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Síndrome de Churg-Strauss/induzido quimicamente , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Eosinofilia/induzido quimicamente , Eosinofilia/complicações , Asma/complicações , Asma/tratamento farmacológicoRESUMO
Lip seal strength and tongue pressure are related to sarcopenia in older adults and are directly linked to the quality of life of workers after retirement. This study examined lip seal strength and tongue pressure among Japanese male workers by age. A self-administered questionnaire survey including alcohol consumption and smoking was conducted on 454 male workers. Height, weight, lip seal strength, and tongue pressure were also measured and then stratified by age (20s, 30s, 40s, 50s, and 60s and over). The mean (25th, 75th percentiles) lip seal strength and tongue pressure for all workers were 13.7 N (11.6, 16.4) and 41.7 kPa (35.2, 48.2), respectively. Both lip seal strength and tongue pressure were lowest in the 20s, at 12.1 N (9.6, 14.0) and 40.6 kPa (33.4, 47.6), respectively. The multiple regression analysis adjusted for smoking showed a significant positive association between lip seal strength and BMI for the 20s, 50s, and 60s and over, and a significant positive association between tongue pressure and BMI for the 30s, 40s, 50s, and 60s and over. To maintain oral health in older adults, it may be useful to measure workers' lip seal strength and tongue pressure and intervene at an earlier stage.
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Lábio , Língua , Idoso , Humanos , Masculino , População do Leste Asiático , Pressão , Qualidade de Vida , SarcopeniaRESUMO
BACKGROUND Primary ciliary dyskinesia (PCD) is a rare genetic disease associated with abnormalities in the structure and function of cilia. The common clinical presentation of PCD is characterized by otitis media, chronic rhinosinusitis (CRS), chronic bronchitis, and infertility due to impaired ciliary motility. PCD is a complex disease and its diagnosis is complicated. However, there are some clinical features that are strong indicators of PCD, namely situs inversus, chronic otitis media, CRS, and chronic bronchitis with wet cough. CASE REPORT A 49-year-old male who had already received 3 operations for refractory CRS presented with nasal discharge, post nasal discharge, and chronic wet cough. Since childhood, he had suffered from otitis media, rhinosinusitis, and bronchitis. He also had a family history of CRS. He was diagnosed as having male infertility at another hospital, but the details were unknown. We performed a fourth surgery and obtained the nasal mucosa for electron microscope analysis during the operation. The transmission electron microscopic findings of the nasal cilia revealed several abnormalities in structure including a central complex defect, microtubular disorganization, and an inner dynein arm defect. Based on these findings and clinical courses, we made the definitive diagnosis of PCD. CONCLUSIONS When faced with refractory CRS cases with characteristic clinical symptoms that are associated with otitis media, chronic bronchitis, and infertility, clinicians should consider the possibility of PCD.
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Síndrome de Kartagener , Sinusite , Situs Inversus , Criança , Doença Crônica , Cílios , Humanos , Síndrome de Kartagener/complicações , Síndrome de Kartagener/diagnóstico , Masculino , Pessoa de Meia-Idade , Sinusite/diagnósticoRESUMO
BACKGROUND An elongated styloid process occurs with Eagle syndrome and causes a variety of symptoms. Fracture of the elongated styloid process is a rare condition. With spontaneous fractures, appropriate treatment cannot be performed in many cases due to unexplained symptoms and indefinite complaints that are not thoroughly examined. CASE REPORT We encountered a case of fractured elongate styloid process reaching the hyoid bone. Based on the findings from cervical 3-dimensional computed tomography (3D-CT), we chose surgery using the transcervical approach instead of the intraoral approach. Symptoms resolved following surgery. CONCLUSIONS A fractured styloid process is a rare event, but it needs to be recognized. If drug therapy does not work, surgical treatment is needed and has been shown to be effective. Surgical therapies include an intraoral approach and a transcervical approach. In the case presented here, 3D-CT was very useful for diagnosis and surgery selection.
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Ossificação Heterotópica , Humanos , Osso Hioide/diagnóstico por imagem , Osso Hioide/cirurgia , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/cirurgia , Osso Temporal/anormalidades , Osso Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) are accepted to be important molecules in the development and maintenance of allergic diseases. Although several types of histamine H(1) receptor antagonist (antihistamine) have been developed and used for the treatment of allergic diseases, the influence of antihistamines on TARC and MDC production is not well understood. OBJECTIVE: The present study was undertaken to examine the influence of antihistamines on TARC and MDC production from CD14+ cells after antigenic stimulation in vitro. METHODS: CD14+ cells prepared from patients with pollinosis to Japanese cedar pollen were stimulated with specific allergen extracted from Japanese cedar pollen (Cry j 1) in the presence of azelastine (AZE), ketotifen (KET), fexofenadine (FEX) and oxatomide (OXA) for 6 days. TARC and MDC levels in culture supernatants were examined by ELISA. We also examined the influence of FEX on TARC and MDC mRNA expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and transcription factor activation in CD14+ cells after Cry j 1 stimulation. RESULTS: FEX at 250 ng/ml, which is almost equal to therapeutic blood levels, caused a significant inhibition of TARC and MDC production.However, AZE, OXA and KET required higher concentrations than their therapeutic blood levels to suppress production of these factors. FEX at 250 ng/ml also suppressed NF-κB activation, phosphorylation of p38 MAPK and extracellular signal-regulated kinases 1 and 2 and expression of mRNA for TARC and MDC. CONCLUSIONS: These results suggest that antihistamines, especially FEX, suppress CC chemokine production from CD14+ cells through interference with antigen-mediated signaling and result in favorable modification of allergic disease states or conditions.
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Quimiocina CCL17/metabolismo , Quimiocina CCL22/metabolismo , Antagonistas dos Receptores Histamínicos H1/farmacologia , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Rinite Alérgica Sazonal/imunologia , Adulto , Antígenos de Plantas/imunologia , Proliferação de Células/efeitos dos fármacos , Quimiocina CCL17/genética , Quimiocina CCL22/genética , Clorfeniramina/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator de Transcrição GATA1/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Histamina/farmacologia , Humanos , Cetotifeno/farmacologia , Leucócitos Mononucleares/citologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Ftalazinas/farmacologia , Piperazinas/farmacologia , Proteínas de Plantas/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Terfenadina/análogos & derivados , Terfenadina/farmacologia , Tuberculina/imunologia , Adulto JovemRESUMO
BACKGROUND: Low-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. Since there is growing evidence that macrolide antibiotic-resistant bacteria's spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin (CAM) and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts (NPFs) through the choice of nitric oxide (NO), which is one of important effector molecule in the development of airway inflammatory disease in vitro. METHODS: NPFs (5 × 105 cells/ml) were stimulated with 1.0 µg/ml lipopolysaccharide (LPS) in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-κB activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively. RESULTS: The addition of CAM (> 0.4 µg/ml) and M-4 (> 0.04 µg/ml) could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-κB activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 µg/ml of the agent was added to cell cultures. CONCLUSION: The present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.