Tratamiento a medida en paciente con recurrencia tardía locorregional Hospital Alemán Unidad de Mastología / Tailored treatment in patient with Locoregional late recurrence

Introducción: Entendemos por recurrencia tardía del cáncer de mama (CM) a la enfermedad que aparece nuevamente después de más de 5,10 o incluso más de 20 años. En mujeres con tumores con receptor de estrógeno (RE) positivo y HER2 negativo, al menos la mitad de las recurrencias ocurren luego de 5 años después del diagnóstico primar Las recurrencias posteriores a mastectomía pueden comprometer la pared torácica, la piel o los ganglios linfáticos regionales. Las recurrencias invasivas pueden ser localizadas o difusas e involucrar la piel, los tejidos subcutáneos, la musculatura torácica o el tejido blando extraganglionar. Las recurrencias en los ganglios mamarios interno e infraclavicular son poco frecuentes, alrededor del 1,5%, mas allá de que estos ganglios son el segundo sitio de drenaje linfático en el CM Los tratamientos extendidos y más efectivos contra el CM han aumentado la prevalencia de sobrevivientes a largo plazo y con ello un retraso en el tiempo de recaída, mucho más marcado en los tumores de tipo luminal. En este reporte de caso nos abocamos a este tipo de pacientes, cómo es su diagnóstico y cuáles fueron sus tratamientos. Objetivo: Reportar mediante un caso clínico el manejo individualizado de una paciente con antecedente de CM y recurrencia tardía locorregional(AU)

Practice-Changing Use of the 21-Gene Test for the Management of Patients With Early-Stage Breast Cancer in Latin America.

PURPOSE: We present a physician survey of the impact of 21-gene Breast Recurrence Score test results on treatment decisions in clinical practice in Latin America. METHODS: This prospective survey enrolled consecutive patients at 14 sites in Argentina, Colombia, Mexico, and Peru who had routine 21-gene testing. Physician surveys captured patient and tumor characteristics and treatment decisions before and after 21-gene test results. The survey spanned the period before and after Trial Assigning Individualized Options for Treatment (TAILORx) results reported (June 2018). Overall net percent change in adjuvant chemotherapy recommendations was estimated, and asymptotic 95% CIs with continuity correction were calculated. The proportion with a change between pretest treatment recommendation and actual treatment received was calculated overall and by Recurrence Score groups per TAILORx. RESULTS: Between March 2015 and December 2019, the survey was completed for 647 patients; 20% were node-positive. The mean patient age was 54 years (24-85 years); 55% were postmenopausal; 17%, 63%, and 20% had grade 1, 2, and 3 tumors, respectively; and 30% had tumors > 2 cm. Recurrence Score (RS) results were as follows: 20% RS 0-10, 56% RS 11-25, and 24% RS 26-100. Overall, chemotherapy recommendations fell by a relative proportion of 39% (95% CI, 33.4 to 44.3) after 21-gene testing (33% decrease in node-negative and 55% decrease in node-positive). Among node-negative patients, the relative decrease in chemotherapy recommendations was 28% (95% CI, 18.9 to 39.5) before TAILORx and 36% (95% CI, 28.4 to 43.7) after. CONCLUSION: To our knowledge, this large survey of 21-gene test practice patterns was the first conducted in Latin America and showed the relevance of 21-gene testing in low- and medium-resource countries to minimize chemotherapy overuse and underuse in breast cancer. The results showed substantial reductions in chemotherapy use overall-especially after TAILORx reported-indicating the practice-changing potential of that study.

Asociación del antígeno ki67 y otros factores clínico patológicos con el Score de Oncotype DX en carcinomas luminales de mama / Association of the ki67 antigen and other clinicopathological factors with the Oncotype DX Score in luminal breast carcinomas

Introducción: Los tumores luminales presentan diferencias moleculares y distinto comportamiento. El antígeno ki67 (ki67) es uno de los factores que sirve para diferenciar entre luminal A y B. Las plataformas genómicas pueden identificar qué pacientes se benefician con quimioterapia. Objetivo: Establecer si existe asociación entre ki67 y Score de Oncotype Dx o score de recurrencia (SR). Evaluar la influencia del ki67 y el SR en la decisión terapéutica, evaluar la asociación entre riesgo clínico y SR, entre invasión linfovascular (ILV) y SR y entre axila positiva (hasta 1 ganglio) y SR. Material y método: Estudio retrospectivo, observacional, descriptivo. Se incluyeron 68 pacientes con tumores luminales Her2Neu negativos, T1-T2, axila negativa o positiva hasta 1 ganglio las cuales realizaron Oncotype DX entre 2009 y 2020 en el Hospital Alemán. Se clasificaron en SR menor o igual a 25 y mayor a 25 en base al estudio TAILORX donde se demostró que globalmente no hay beneficio con quimioterapia entre 0-25. Resultados: Se observó asociación entre ki67 y SR en 44 (64,7%) pacientes y fue mayor entre ki67 bajo y SR menor o igual a 25 (77,3%). El tratamiento se basó en el SR. Se observó asociación entre riesgo clínico y SR en 43 (63,2%) pacientes y fue mayor entre bajo riesgo clínico y SR menor o igual a 25 (87,5%). En un 88,8% no existió asociación entre ILV y SR, como así tampoco, entre axila positiva hasta 1 ganglio y SR en un 85,7%. Conclusiones: Es menester ofrecer a toda paciente con un tumor luminal una plataforma genómica ya que tanto el ki67 como otros factores clínicopatológicos por sí solos no demostraron ser superiores ni suficientes.

Introduction: Luminal tumors show molecular differences and different behavior. The antigen ki67 (ki67) is one of the factors that differentiate between luminal A and B. Genomic platforms can identify which patients will benefit from chemotherapy. Objective: To establish if there is an association between ki67 and Oncotype Dx Score or recurrence score (RS). To assess the influence of ki67 and RS on the therapeutic decision, to evaluate the association between clinical risk and RS, between lymphovascular invasion (LVI) and RS, and between positive armpit (up to 1 node) and RS. Material and method: Retrospective, observational, descriptive study. We included 68 patients with negative Her2Neu luminal tumors, T1-T2, negative or positive axillary up to 1 node, who performed Oncotype DX between 2009 and 2020 at Hospital Alemán. They were classified into RS less than or equal to 25 and greater than 25 based on the TAILORX study, where it was shown that overall there is no benefit from chemothe- rapy between 0-25. Results: An association was observed between ki67 and RS in 44 (64.7%) patients and it was greater between low ki67 and RS less than or equal to 25 (77.3%). The treatment was based on RS. An association between clinical risk and RS was observed in 43 (63.2%) patients, and it was greater between low clinical risk and RS less than or equal to 25 (87.5%). In 88.8% there was no association between LVI and RS, as well as between positive axillary up to 1 node and RS in 85.7%. Conclusions: It is necessary to offer every patient with a luminal tumor a genomic platform since both ki67 and other clinicopathological factors alone did not prove to be superior or sufficient.

Novel clinical scores for occupational asthma due to exposure to high-molecular-weight agents.

OBJECTIVE: Specific inhalation challenge (SIC) as the reference diagnostic test for occupational asthma (OA) is not widely available worldwide. We aimed to develop non-SIC-based models for OA. METHODS: Of 427 workers who were exposed to high-molecular-weight agents and referred to OA clinic at Montréal Sacré-Cœur Hospital between 1983 and 2016, we analysed 160 workers who completed non-specific bronchial hyper-responsiveness (NSBHR) tests and still worked 1 month before SIC. OA was defined as positive SIC. Logistic regression models were developed. The accuracy of the models was quantified using calibration and discrimination measures. Their internal validity was evaluated with bootstrapping procedures. The final models were translated into clinical scores and stratified into probability groups. RESULTS: The final model, which included age ≤40 years, rhinoconjunctivitis, inhaled corticosteroid use, agent type, NSBHR, and work-specific sensitisation had a reasonable internal validity. The area under the receiver operating characteristics curve (AUC) was 0.91 (95% CI 0.86 to 0.95), statistically significantly higher than the combination of positive NSBHR and work-specific sensitisation (AUC=0.84). The top 70% of the clinical scores (ie, the high probability group) showed a significantly higher sensitivity (96.4%vs86.9%) and negative predictive value (93.6%vs84.1%) than the combination of positive NSBHR and work-specific sensitisation (p value <0.001). CONCLUSIONS: We developed novel scores for OA induced by high-molecular-weight agents with excellent discrimination. It could be helpful for secondary-care physicians who have access to pulmonary function test and allergy testing in identifying subjects at a high risk of having OA and in deciding on appropriate referral to a tertiary centre.

Análisis retrospectivo en Carcinoma Ductal In Situ. Experiencia de 11 años / Retrospective Analysis in In Situ Ductal Carcinoma. A 11 years experience

Objetivo El objetivo del trabajo es describir la experiencia del Servicio de Mastología del Hospital Alemán de Buenos Aires en el diagnóstico, tratamiento y seguimiento del Carcinoma Ductal In Situ (cdis) de la mama. Material y método Se analizan retrospectivamente 953 carcinomas de mama tratados en el Servicio de Mastología del Departamento de Ginecología y Obstetricia del Hospital Alemán de Buenos Aires, entre enero de 2004 y diciembre de 2014. Resultados Se identificaron 206 biopsias (brq 25; Mammotome 151; core biopsia 30) de Carcinomas Ductales In Situ. Luego de su evaluación anatomopatológica definitiva, del total de las 953 pacientes analizadas, 172 (18%) resultaron Carcinomas Ductales In Situ puros. En cuanto al informe imagenológico, de esas 206 pacientes, el 80,1% presentó microcalcificaciones. El diagnóstico de Carcinoma In Situ fue realizado en 181 (87%) pacientes por procedimientos microinvasivos preoperatorios y en las 25 (13%) pacientes restantes por Biopsia Radioquirúrgica (brq). Se evidenció un 18,8% de subdiagnóstico luego de procedimientos microinvasivos. En nuestra casuística el 84,3% fue gh3/gh2 mientras que el 15,7% resultó gh1. Al comparar en las piezas quirúrgicas el tamaño y correlacionarlo con los 34 casos de carcinoma invasor y microinvasor, se observó el 54,8% de invasión en aquellos tumores mayores a 30 mm, el 50,4% en aquellos que superaron los 21 mm y ningún caso en los tumores menores a 10 mm. El 20% de las lesiones multicéntricas se asoció a tumor invasor. Se practicó técnica de ganglio centinela en 23,8% pacientes en primera cirugía, resultando negativo en todos los casos. En cuanto al tratamiento radiante y hormonal, se determinó que se realizó radioterapia en 131 pacientes (85,6%) y tratamiento hormonal en el 75%. En el seguimiento hasta diciembre de 2014 se registraron 11 recaídas (5,23%) Conclusiones El porcentaje de cdis del 18% presentado en nuestra casuística y los resultados comparativos coinciden con lo publicado en la literatura indexada.

Objective To describe our experience in the diagnosis, treatment and follow up of patientes with Ductal Carcinoma In Situ (dcis). Materials and method A total of 953 patients with breast cancer were treated in the Breast Cancer Unit of the Hospital Alemán of Buenos Aires, from January 2004 until December 2014. Results dcis was identified in 206 patients (25 by surgical excision, 151 by Mammotome and 30 by core biopsy). After final pathological evaluation, 172 (18%) resulted in pure dcis. Of the 206 patients diagnosed with dcis, 80,1% presented with microcalcifications on breast imaging studies and 181 (87%) patients were diagnosed through preoperative microinvasive procedures and 25 (13%) through surgical excision. Microinvasive procedures showed a 18,8% of subdiagnosis. 84,3% were Grade 3/2 and 15,7% were Grade 1 tumors. Compared with the 34 patients diagnosed with invasive and microinvasive carcinomas, invasion was observed in 54,8% in tumors over 30 mm, 50,4% in those over 21 mm and none in tumors less than 10 mm. 20% of multicentric carcinomas were associated with invasive tumors. Sentinel lymph node technique was performed in 23,8% of patients and none resulted positive. Radiotherapy was performed in 131 (85,6%) cases, and 75% received hormonal treatment. Until December 2014, 11 (5,53%) recurrences were diagnosed. Conclusions Our results as to diagnosis, treatment and recurrence rate pure of dcis are consistent with the international indexed literature.

¿Es posible identificar factores pronósticos y predictivos en Cáncer de Mama Triple Negativo? / Is it possible to identify prognostic and predictive factors in Triple Negative breast cancer?

Introducción Debido a su negatividad para los receptores hormonales y de her2, los cánceres de mama Triple Negativos (cmtn) no tienen tratamiento específico y es la quimioterapia la única modalidad de tratamiento sistémico. Objetivos El objetivo de este trabajo es, en primer lugar, evaluar en los cmtn la factibilidad de utilizar a la infiltración linfocitaria y a la expresión de la proteína p53 y de los receptores de andrógenos como marcadores pronósticos (sobrevida global y período libre de enfermedad), y, en segundo lugar, determinar su utilidad como elementos predictivos de respuesta a la quimioterapia. Material y método Analizamos un grupo de pacientes con diagnóstico de cmtn tratadas en el Hospital Alemán de Buenos de Aires y en el Sanatorio Mater Dei desde diciembre de 2000 a diciembre de 2012. Resultados Se analizaron 21 pacientes con cmtn. En nuestra población, la quimioterapia se asoció con menor riesgo de recaída y mortalidad. La prevalencia en la expresión de la proteína p53 fue del 61,9% en la población general, del 72,7% en las recaídas y del 66,6% en las pacientes fallecidas. El 23,8% de las pacientes estudiadas presentó expresión de receptores androgénicos. La infiltración linfocitaria tumoral (tils) promedio fue del 20,5% (5% - 60%), siendo menor cuando se evalúa exclusivamente la población de pacientes que recayeron (17,7%) y aún menor cuando se evalúa la población de pacientes fallecidas (11,7 %). Discusión La quimioterapia tuvo un rr de sobrevida de 0,15 (ic: 0,06 - 0,78) con una p: 0,0021. La expresión de la proteína p53 tuvo un rr de 1,2 como factor de riesgo de mortalidad o progresión (ic: 0,23 - 9,07; p: 0,6). La expresión de receptores androgénicos tiene un rr de 1,6 como factor de riesgo de mortalidad o progresión (ic: 0,21 - 6,24; p: 0,41). La presencia de tils mayor al 20% es predictora de mortalidad y recurrencia con una p: 0,023. Conclusiones La determinación de tils junto con la evaluación en la expresión de la proteína p53 son herramientas útiles a la hora de definir la conveniencia de un tratamiento quimioterápico ya que ambas se asocian con aumento de la sobrevida total y de la sobrevida libre de enfermedad, aunque en nuestra población esta asociación no haya sido estadísticamente significativa para la p53 y sí para la presencia de tils

Introduction Because of its negativity for hormonal and her2 receptors, Triple Negative tumors do not benefit from anti hormonal treatments or with anti her2. They have no specific treatment and chemotherapy being the only form of systemic treatment. Objectives The objective of this study is, first, to evaluate in Triple Negative tumors feasibility of using lymphocyte infiltration, the expression of p53 protein and androgen receptors as prognostic markers (overall survival and disease-free), and, second, evaluate their usefulness as predictors of response to chemotherapy. Materials and method We intend to analyze those patients diagnosed with tnbc treated at the German Hospital of Buenos Aires and at the Mater Dei Sanatorium from December 2000 to December 2012. Results Twenty-one patients with tnbc were analyzed. In our population, chemotherapy was associated with a lower risk of relapse and mortality. The prevalence in the p53 mutation was 61.9% in the general population, 72.7% in relapses and 66.6% in deceased patients. Tumor lymphocytic infiltration (tils) on average was 20.5% (5% - 60%), being lower when only the population of patients who relapsed were evaluated (17.7%), and even lower when evaluating the population of deceased patients (11.7%). Discussion Chemotherapy had a survival rr of 0.15 (ci: 0.06 - 0.78) with a p: 0.0021. The p53 protein mutation had a rr of 1.2 as a risk factor for mortality or progression (ci: 0.23 - 9.07; p: 0.6). The expression of androgen receptors has a rr of 1.6 as a risk factor for mortality or progression (ci: 0.21 - 6.24; p: 0.41). The presence of tils greater than 20% is a predictor of mortality and recurrence with a p: 0.023. Conclusions The determination of tils together with determination of the p53 protein mutation are useful tools in determining the suitability of a chemotherapeutic treatment since both are associated with increased total survival and disease-free survival, although in our population this association was not statistically significant for p53.

Influencia del score de recurrencia Oncotype Dx en la decisión del tratamiento adyuvante del cáncer de mama / Influence of Oncotype Dx recurrence score in the decision of the adjuvant treatment of breast cancer

Objetivos El objetivo primario del presente estudio es analizar cómo la utilización del ensayo Oncotype Dx modifica y condiciona la elección del tratamiento adyuvante. En segundo lugar, nos propusimos evaluar la evolución de aquellas pacientes con score de recurrencia menor a 10, las cuales han sido clasificadas en el ensayo clínico TailorX como pacientes de bajo riesgo pasibles de ser tratadas solo con terapia hormonal adyuvante Por último, buscamos evaluar si existe correlación entre el valor de Ki 67, la invasión linfovascular (ILV) y el score del Oncotype Dx. Material y método Analizamos retrospectivamente 62 pacientes con cáncer de mama con receptores hormonales positivos, her2 Neu negativo y ganglios negativos, a las cuales se les solicitó el score de recurrencia Oncotype Dx, y comparamos con las indicaciones de terapia adyuvante surgidas previamente de factores de riesgo clínicos y anátomo-patológicos. Resultados Treinta pacientes (48,4%) presentaron score de bajo riesgo, 25 (40,3%) score de riesgo intermedio y las 7 restantes (11,3%) score de alto riesgo de recurrencia. Analizando el cambio de conducta, una vez obtenido el resultado del Oncotype Dx, encontramos un cambio de decisión en 16 pacientes (26%). Según la indicación de los factores de riesgo clínicos y anátomo-patológicos, de las 62 pacientes incluidas en este estudio, se había indicado adyuvancia con quimioterapia y hormonoterapia a 26 pacientes y hormonoterapia solamente a las 36 pacientes restantes. Posterior a la realización del Oncotype Dx, de las 26 pacientes a las cuales se les había indicado quimioterapia, en 12 se modificó el tratamiento a adyuvancia hormonal solamente (46,15% de reducción de la indicación en este grupo). Por otra parte, en aquellas 36 pacientes respecto de las cuales nuestra indicación previa había sido solamente adyuvancia hormonal, el resultado del Oncotype Dx determinó la realización de quimioterapia en 4 (11,1%). Cotejando la correlación entre Oncotype Dx y factores anátomo-patológicos, encontramos como dato interesante que todas aquellas pacientes con score de alto riesgo presentaban Ki 67 elevado, pero no a la inversa, mientras que no hallamos relación entre invasión linfovascular (ilv) presente y Oncotype Dx elevado. Conclusiones Consideramos que la utilización de plataformas genómicas como el Oncotype Dx es un elemento útil a la hora de tomar decisiones sobre el tratamiento adyuvante del carcinoma de mama Luminal con ganglios negativos, donde la indicación de la quimioterapia adyuvante debe ser cuidadosamente evaluada.

Objectives The primary objective is to analyze how the use of Oncotype Dx modifies and conditions the choice of adjuvant treatment. Second, to evaluate the evolution of those patients with score of recurrence <10 ­of low risk in TailorX Clinical Trial­, treatable with hormonal adjuvancy only. Finally, compare correlation between lymphovascular invasion (ilv), Ki 67 and Oncotype High Dx. Materials and method We retrospectively analyzed 62 breast cancer patients with hormone receptor positive, hers Neu negative and negative lymph nodes, who were asked for the Oncotype Dx recurrence score and compared with the indications for adjuvant therapy that had previously arisen from clinical and anatomic risk factors pathological. Results Thirty patients (48.4%) presented a low risk score, 25 patients (40.3%) intermediate risk and the remaining 7 patients (11.3%), a high risk score for recurrence. Once the Oncotype Dx result was obtained, we found a decision change in 16 patients (26%). According to the indication of the clinical and anatomopathological risk factors, of the 62 patients included in this study, adjuvancy had been indicated with chemotherapy and hormone therapy to 26 patients and only hormone therapy to the remaining 36 patients. After the Oncotype Dx, of the 26 patients to whom chemotherapy had been indicated, in 12 of them the treatment was modified to hormonal adjuvancy only (46.15% reduction of the indication in this group). On the other hand, in those 36 patients that our previous indication had been only hormonal adjuvancy, the result of the Oncotype Dx determined the accomplishment of chemotherapy in 4 of them (11.1%). Comparing the correlation between Oncotype Dx and anatomopathological factors, we found that all those patients with a high risk score had elevated Ki 67, but not inversely, whereas we did not find a relation between present lymphovascular invasion (ilv) and Oncotype High Dx. Conclusions We believe that the use of genomic platforms such as Oncotype Dx is a useful element when making decisions about the adjuvant treatment of Luminal breast cancer with negative ganglia, where the indication of adjuvant chemotherapy should be carefully evaluated.

Diagnostic Accuracy of Inflammatory Markers for Diagnosing Occupational Asthma.

BACKGROUND: The assessment of airway responsiveness and inflammation is key to the investigation of occupational asthma (OA). OBJECTIVE: We sought to assess and compare the diagnostic accuracies of the blood and sputum eosinophil counts and the methacholine challenge for the diagnosis of OA. METHODS: We conducted a retrospective study assessing 618 patients who underwent specific inhalation challenges (SICs) for symptoms suggestive of OA between 2000 and 2015. A sputum induction and a methacholine challenge were performed before and after SICs. Blood samples were collected in all subjects before the SICs and in 100 subjects before and after SICs. The diagnostic accuracies of blood and sputum eosinophil counts and methacholine challenge were calculated for diagnosing OA. RESULTS: The change in blood eosinophil count failed to differentiate workers with positive and negative SICs. The change in sputum eosinophil counts induced by the exposure to the offending agent had the highest diagnostic accuracy (receiver operating characteristic area under the curve: 86% [95% confidence interval: 0.8-0.9, P < .001]) for diagnosing OA compared with changes in concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 second (PC20) and blood eosinophils. Combining a 2-fold or greater decrease in PC20 or a 3% or greater increase in sputum eosinophil count achieved a sensitivity of 84% and a specificity of 74% with a negative predictive value of 91% for the diagnosis of OA. CONCLUSIONS: Blood eosinophil counts do not appear to be an effective aid for diagnosing OA. The performance of both sputum cell count analysis and a methacholine challenge before and after exposure to the offending agent may represent an effective alternative in diagnosing OA when SICs are unavailable.

Systemic inflammatory markers as independent prognosticators of head and neck squamous cell carcinoma.

BACKGROUND: The purpose of this study was to investigate the prognostic value of the pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: We conducted a retrospective analysis of patients diagnosed with HNSCC at McGill University Health Center from 2000 to 2011 (273 patients were retained). Hematologic parameters were recorded within 4 weeks of diagnosis. Mortality and recurrence rates were compared according to various PLR and NLR thresholds. RESULTS: Of the total patients, 20.5% died and 11.0% had disease recurrence. PLR >170 was associated with higher mortality (p = .008). The subgroup with a combination of PLR >170 and NLR ≤3.0 was associated with higher T classification and highest mortality (43%). NLR above 4.2 predicted higher rates of recurrence (p < .0001). The NLR/PLR combination was at least as good as TNM staging in predicting survival. CONCLUSION: PLR is an independent predictor of mortality; NLR is an independent predictor of recurrence in HNSCC. These parameters might be used to identify advanced stages rapidly and economically.

Occupational rhinitis due to steel welding fumes.

Exposure to welding fumes is a recognized respiratory hazard. Occupational asthma but not occupational rhinitis has been documented in workers exposed to steel welding fumes. We report a 26-year-old male with work-related rhinitis symptoms as well as lower airways symptoms suggestive of occupational asthma and metal fume fever associated with exposure to steel welding fumes. The diagnosis of occupational rhinitis was confirmed by specific inhalation challenge.

Specific inhalation challenge with flour induced release of brain-derived neurotrophic factor in nasal fluid.

BACKGROUND: Neurotrophins may play a role in the pathophysiology of allergic occupational rhinitis (OR). We sought to investigate whether an immediate allergic reaction that induces nasal inflammation is also able to induce changes in levels of brain-derived neurotrophic factor (BDNF) in nasal lavage (NAL) fluid from patients with allergic OR. METHODS: Ten patients sensitized to flour underwent control and active specific inhalation challenge (SIC) on consecutive days. Nasal response to SIC was monitored with acoustic rhinometry and symptoms recording. NAL was performed before and 30 minutes, 6 hours, and 24 hours after control and active challenge for the assessment of levels of BDNF and inflammatory cells in NAL fluid. RESULTS: In contrast to control day, flour challenge induced immediate clinical reactions in all subjects. After flour challenge, a significant increase in levels of BDNF in NAL fluid was observed at 6 hours after challenge (p < 0.05). Also, a significant increase in the number of eosinophils in NAL fluid at 30 minutes (p < 0.01), 6 hours (p < 0.01), and 24 hours (p = 0.05) postchallenge was observed. Also, levels of BDNF in NAL fluid were significantly higher at 30 minutes after flour challenge (p = 0.02) in comparison to levels on the control day at the same postchallenge time. A marginally significant positive correlation between BDNF levels and eosinophil counts at 30 minutes (r = 0.60, p = 0.06) and at 6 hours (r = 0.50, p = 0.08) after flour challenge was noted. CONCLUSION: We showed that BDNF is released in nasal fluid after SIC with flour. Results support the suggestion that neurotrophins may play a role in the pathogenesis of allergic OR.

Challenge exposure to isocyanates induces changes in nasal patency in patients reporting work-related respiratory symptoms.

OBJECTIVE: To examine the utility of specific inhalation challenge (SIC) in assessing the nasal congestive response to isocyanate exposure. METHODS: Nine patients complaining of work-related respiratory symptoms underwent SIC with exposure to isocyanate for 4 and 120 minutes on different days. Nasal volume was monitored by acoustic rhinometry and nasal congestion by the visual analogue scale (VAS) for up to 6 hours. RESULTS: The 4-minute isocyanate SIC induced a nonsignificant fall in nasal volume and no increase in the VAS score. The 120-minute isocyanate SIC induced a significant fall in nasal volume at 15, 30, and 60 minutes postchallenge that was associated with a significant increase in the VAS score at 15 and 30 minutes postchallenge. CONCLUSIONS: SIC appears useful to assess changes in nasal patency after exposure to isocyanate. Exposure to isocyanates can induce nasal congestion that can be objectively monitored during SIC.

Prospective outcome assessment of occupational rhinitis after removal from exposure.

OBJECTIVE: To conduct a prospective evaluation of clinical and quality of life (QOL) outcomes of occupational rhinitis (OR) after cessation of exposure. METHODS: We assessed changes in nasal symptoms, disease-specific QOL, nasal patency, and nasal inflammation in 20 subjects with confirmed OR. Olfactory function was assessed cross-sectionally at follow-up. RESULTS: At follow-up, a significant decrease in the number of nasal symptoms and a significant improvement in QOL were observed. There were no significant differences in nasal patency outcomes. A not significant decrease in neutrophils number in nasal fluid and a significant decrease in macrophages were observed. As a group, study subjects showed a mild olfactory dysfunction at follow-up. CONCLUSIONS: We showed that cessation of exposure to causal agent improved QOL in patients with OR, leading to relief of rhinitis-associated symptoms and improvement in well-being.

Matrix metalloproteinase-9 increases in the sputum from allergic occupational asthma patients after specific inhalation challenge.

BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a role in the pathogenesis of asthma. MMP-9 increases in the sputum of asthmatic patients after bronchial challenge with common allergens. We sought to assess whether a high-molecular-weight occupational allergen was able to induce changes in MMP-9 as well as in other MMPs and TIMPs in subjects with occupational asthma. METHODS: Ten patients underwent specific inhalation challenge (SIC) on 2 consecutive days. We monitored changes in lung function by measuring FEV(1) for 7 h. Induced sputum test was performed at 6 h after sham and flour challenge. The total and differential cell counts were analyzed. Levels of MMPs (specifically MMP-2, MMP-7, MMP-9 and MMP-13) were measured using Fluorokine® MultiAnalyte Profiling kits and a Luminex® Bioanalyzer, while levels of TIMP-1 and TIMP-2 were measured by ELISA. RESULTS: Flour challenge increased the percentage of eosinophils in sputum samples. Asthmatic reactions induced by flour were associated with a significant increase in the sputum level of MMP-9 (p = 0.05), but not in the levels of MMP-2, MMP-7, MMP-13, TIMP-1 and TIMP-2. Sputum levels of MMP-9 measured after flour challenge were nearly significantly correlated (r = 0.67; p = 0.06) with the maximal fall in FEV(1) observed during the asthmatic reaction, but they did not correlate with the number of neutrophils (r = 0.18; p = 0.7) and eosinophils (r = 0.55; p = 0.2). CONCLUSIONS: This study showed that MMP-9 increases in sputum samples from sensitized occupational asthma patients after SIC with flour.

Integrated approach to diagnosis of associated occupational asthma and rhinitis.

Patients with coexisting work-related rhinitis and asthma would benefit from an adequate and simultaneous recognition of both diseases. The present case illustrates the advantages and importance of using an integrated approach to confirm a diagnosis of occupational rhinitis (OR) and occupational asthma (OA). A 38-year-old woman, who worked as an animal laboratory technician since 2004, first noticed the appearance of rhinitis and conjunctivitis symptoms in 2007 when she was exposed to rats. A skin-prick test with rat extract was strongly positive. A specific inhalation challenge with parallel assessment of nasal and bronchial responses was conducted. After 10 min of exposure, she developed rhinitis and conjunctivitis symptoms, her forced expiratory volume in 1 s dropped by 27.5% and her nasal volume, measured by acoustic rhinometry, decreased by 80% from baseline values. After allergen exposure, induced sputum and nasal lavage examination demonstrated an increase in eosinophils (11% and 20%, respectively). A diagnosis of associated allergic OA and OR was confirmed and she was advised to stop working with rats. A systematic and parallel diagnostic approach enables confirmation of a diagnosis of OA and OR in patients complaining of work-related rhinitis and asthma symptoms.