ANEXO

ANEXO 1

ANEXO 2

TERMO DE CONSENTIMENTO LIVRE E ESCLARECIDO (TCLE)

Eu, ____________________________, ___anos, brasileiro, RG______________, __________, trabalho no Cooperativa Nova Esperança e resido à________________________________________________________, estou sendo convidado a participar de um estudo denominado “Determinação das variações

imunohistoquímicas características da exposição á fibra de algodão na mucosa nasal de pacientes portadores de rinossinusite crônica”. cujos objetivos e

justificativas são: pesquisar os prováveis fatores (Imunohistoquímicos) envolvidos na ocorrência da Rinossinusite entre os trabalhadores que, presumivelmente por estarem expostos à fibra de algodão no ambiente de trabalho, desenvolvem esta patologia tão prevalente na população em geral, mas em especial neste grupo do estudo.

A minha participação no referido estudo será no sentido de permitir a realização dos exames e estudos que se seguirão para confirmar o diagnóstico clínico de RNSC e as conclusões a que o estudo se refere. Durante esta etapa estou ciente que serei submetido à Videoendoscopia Nasal (filmagem com câmera de video especial pela cavidade nasal), Tomografia Computadorizada dos Seios Paranasais (exame de imagem, similar aos RXs) e Realização de retirada de porção pequena da mucosa nasal do corneto médio (sob anestesia local tópica, ou seja, não será necessário injeção de qualquer substância), e este material do meu nariz será armazenado e utilizado para este estudo e outros que se seguirem, se necessário e sempre sob sigilo e tutela da Comissão de Ética Médica da USP-RP.

Fui alertado de que, da pesquisa a se realizar, posso esperar como benefício o aprofundamento do conhecimento de meu quadro clínico, ou seja, a real situação da minha doença – Rinossinusite Crônica, se realmente comprovada.

Recebi, por outro lado, os esclarecimentos necessários sobre os possíveis desconfortos e riscos decorrentes do estudo, levando-se em conta que é uma pesquisa, e os resultados positivos ou negativos somente serão obtidos após a sua realização. Assim, estou ciente que durante a realização dos exames é possível ocorrer algum desconforto e até mesmo pequenos sangramentos nasais, sempre em pequena quantidade e de fácil resolução.

Estou ciente de que minha privacidade será respeitada, ou seja, meu nome ou qualquer outro dado ou elemento que possa, de qualquer forma, me identificar, será mantido em sigilo.

Também fui informado de que posso me recusar a participar do estudo, ou retirar meu consentimento a qualquer momento, sem precisar justificar, e de, por desejar sair da pesquisa, não sofrerei qualquer prejuízo.

O pesquisador envolvido com o referido projeto é o Dr. Ivan de Picoli Dantas, Pós Graduando da Faculdade de Medicina de Ribeirão Preto - USP (Universidade de

São Paulo), o telefone de contato é 19-34069003 e o da Instituição é 16-36022862, o e-mail para contato é [email protected], e com ele poderei manter contato à qualquer instante para assuntos e dúvidas relacionadas ao estudo.

É assegurada a assistência durante toda pesquisa, bem como me é garantido o livre acesso a todas as informações e esclarecimentos adicionais sobre o estudo e suas consequências, enfim, tudo o que eu queira saber antes, durante e depois da minha participação.

Enfim, tendo sido orientado quanto ao teor de todo o aqui mencionado e compreendido a natureza e o objetivo do já referido estudo, manifesto meu livre consentimento em participar, estando totalmente ciente de que não há nenhum valor econômico, a receber ou a pagar, por minha participação.

No entanto, caso eu tenha qualquer despesa decorrente da participação na pesquisa, haverá ressarcimento na forma seguinte: apresentarei os recibos e ou tickets de passagens de transporte e o Dr. Ivan fará o ressarcimento em espécie. De igual maneira, caso ocorra algum dano decorrente da minha participação no estudo, serei devidamente indenizado, conforme determina a lei.

Americana, de de 2010

__________________________________________

Nome e assinatura do sujeito da pesquisa

___________________________________________ Dr. Ivan de Picoli Dantas – Pesquisador Responsável

ANEXO 3

QUESTIONÁRIO

Nome: ________________________________ Idade: _____

Sexo: ______

Função na empresa: _____________ Tempo na função: _____________

Fuma: SIM ( ) NÃO ( )

Você tem Sinais ou Sintomas Sugestivos de Rinossinusite Crônica?

Assinale SIM apenas se os sintomas abaixo persistem por mais de três meses por ano

- Obstrução/bloqueio/congestão nasal (nariz entupido): SIM ( ) NÃO ( )

- Gotejamento anterior ou posterior- secreção ou catarro escorrendo pela garganta ou pelo nariz constantemente:

SIM ( ) NÃO ( )

- Pressão ou dor facial (dor na cabeça, na face e ou na testa): SIM ( ) NÃO ( )

- Redução/perda do olfato (não sente ou sente pouco cheiro): SIM ( ) NÃO ( )

Nome__________________________________________________________

SNOT-22 - Sino Nasal Outcome Test

Considerando a gravidade e a frequência do sintoma relate cada item, assinalando o número correspondente a como você o sente Não há problema (0) Problema muito suave (1) Problema leve (2) Problema moderado (3) Problema severo (4) Pior problema que pode existir (5) Item(s) mais importante(s)

1. Necessidade de assuar o nariz 2. Espirros

3. Nariz escorrendo 4. Tosse

5. Secreção escorrendo pela garganta

6. Secreção grossa saindo pelo nariz 7. Sensação de ouvido cheio ou

tapado 8. Tontura 9. Dor de ouvido

10. Dor ou pressão no rosto 11. Dificuldade para conseguir dormir 12. Acorda no meio da noite 13. Falta de uma boa noite de sono 14. Acorda cansado

15. Fadiga ou cansaço durante o dia 16. Diminuição do seu rendimento

para realizar atividades do seu dia a dia

17. Diminuição da sua concentracão para realizar atividades do trabalho.

18. Frustrado, agitado ou irritado 19. Tristeza

20. Sensação de vergonha

21. Dificuldade para sentir cheiros ou gostos

QUESTIONÁRIO RINITE

Nome: _____________________________ Idade: _____ Sexo: _____

Função na empresa: _____________ Tempo na função: __________

Você tem Sinais ou Sintomas de RINITE?

Por favor, responda as perguntas, abaixo, em relação ao que você sente no seu nariz NA MAIOR PARTE DOS DIAS EM QUE TRABALHA:

- Seu nariz fica muito entupido: SIM ( ) NÃO ( ) - Seu nariz escorre constantemente: SIM ( ) NÃO ( ) - Seu nariz tem coceira: SIM ( ) NÃO ( )

- Você espirra muito: SIM ( ) NÃO ( )

Agora vamos saber o quanto cada um desses sintomas te incomoda, veja como você deve responder:

- se não te incomoda nada marque 0; - se o incomodo diário é leve marque 1;

- se o incomodo diário é moderado, ou seja, nem forte e nem fraco marque 2;

- se seu incomodo diário é forte, grave, que atrapalha a sua vida marque 3; - se o seu incomodo é muito grave, um dos piores problemas para sua vida

marque 4.

NARIZ ENTUPIDO - OBSTRUCÃO NASAL

1. Leve ( ) 2. Moderado ( ) 3. Grave ( ) 4. Muito Grave ( )

NARIZ ESCORRE - RINORREIA

1. Leve ( ) 2. Moderado ( ) 3. Grave ( ) 4. Muito Grave ( )

COCEIRA NO NARIZ

1. Leve ( ) 2. Moderado ( ) 3. Grave ( ) 4. Muito Grave ( )

ESPIRROS

1. Leve ( ) 2. Moderado ( ) 3. Grave ( ) 4. Muito Grave ( )

ANEXO 4

Ivan Picoli Dantas1, Fabiana Cardoso Pereira Valera2, Carlos Eduardo Monteiro Zappelini 3, Wilma Terezinha Anselmo-Lima 2

1

School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto-SP - Brazil, and Santa Casa de Campinas, Campinas, SP, Brazil.

2

Department of Ophthalmology, Otorhinolaryngology Head and Neck Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirâo Preto, SP, Brazil

3

Santa Casa de Campinas, Campinas, SP, Brazil

Author for correspondence:

Ivan De Picoli Dantas, Rua Fonte da Saudade 500, Americana-SP, Brazil, 13471- 613, +551991040400, [email protected]

Abstract

Background: The respiratory tract is one of the main ports of entry of particles and

harmful agents such as gases, vapors or aerosols. Considering that exposure to aerosols may lead to the development of inflammatory processes , which are possible causes of chronic rhinosinusitis (CRS), our objective was to ascertain the prevalence of CRS in workers exposed to cotton dust in order to characterize it as an occupational disease related to this irritant. Casuistic and Methods: This study was based on the analysis of two questionnaires completed by 133 workers of a Textile Industry Cooperative in the main textile production region of São Paulo State, Brazil. The first questionnaire is based on clinical criteria for the diagnosis of CRS according to EPOS, and the second, the Sino-Nasal Outcome Test - 22 (SNOT-22), is a questionnaire adapted from the SNOT-20. Both are internationally validated and easy to use in clinical practice to highlight the impact of chronic rhinosinusitis on the quality of life of patients. Workers with a clinical diagnosis of CRS were subjected to examination by nasal endoscopy and to a CT scan of the sinuses. Results: Among the 133 workers surveyed, 35.3% (n = 47) with clinical symptoms suggestive of CRS were previously selected and were invited to take the additional exams. Of these, 37 were examined, and abnormalities consistent with CRS were found in 67.6% of the nasofibroscopies (n = 25) and in 70.3% (n = 26) of the CT scans. Thus, 19.6% of the entire study population had a diagnostic confirmation of CRS. Discussion: According to the Guide for ENT Occupational Diseases, cotton dust is not cited as a causative agent of rhinosinusitis, but is only related to occupational rhinitis. However, the present study showed that there is an association between this agent and rhinosinusitis. The present study also showed that the diagnostic workup with both CT and endoscopy among patients selected with the questionnaires was effective in confirming the diagnosis of CRS in 70.3% of 37 individuals who did the exams, with a 19.6% prevalence of CRS in the population studied. This rate could have been even higher if the other 10 subjects who fulfilled the clinical criteria of CRS had agreed to take the exams. Conclusion: The high prevalence of CRS in workers exclusively exposed to cotton dust found in this study may characterize this condition as an occupational disease. We also conclude that the questionnaires showed strong sensitivity regarding the symptoms of CRS, which were proven with the additional exams carried out to confirm the disease.

Introduction

The respiratory tract is one of the main sites of entry of foreign particles and substances in the organism. The nasal fossae represent the first contact with the inhaled agents and activate the first defense mechanisms such as filtration, air conditioning and the sensation of odors and irritants. These are important, but usually underestimated, functions.1-4

Because of their location, the nasal fossae are extensively exposed to harmful agents such as gases, vapors or aerodispersoids (dust, smoke, mists, fogs, or cotton fiber itself). These agents may have an uncomfortable (subjective) action or an irritant, allergenic or corrosive (physical events) action. Establishing a correlation between harmful agents present in the work environment and health events of exposed workers should be a constant task in order to provide measures that will avoid or minimize such events.4-6

Rhinosinusitis (RS) is one of the most prevalent affections of the upper airways, with a high financial cost for society. The natural course of the inflammatory processes of the nasal mucosa, whether of irritative or infectious origin (viruses, bacteria, fungi), of allergic origin and of unknown origin such as nasosinusal polyposis, may lead to chronic rhinosinusitis (CRS)2,5,7, which may be defined as any chronic inflammatory process, i.e., a process lasting more than 12 weeks, involving the mucosa lining the nasal cavity and the paranasal sinuses.

CRS is clinically characterized by two or more of the following symptoms: nasal obstruction or anterior or posterior rhinorrhea, facial pain/pressure and reduction or loss of olfaction for at least 12 weeks, endoscopic signs of nasal polyps and/or mucupurulent rhinorrhea in the middle meatus and/or mucosal edema or primary obstruction of the ostiomeatal complex (OMC), in addition to tomographic changes showing blockade of the OMC and/or paranasal sinuses.2,3,4,5,9,10,11

Prevention is a basic attitude regarding CRS, starting with information and guidance for the patient with respect to environmental control, particularly in atopic patients. Environmental vigilance as a form of prevention is based on the control and attenuation of exposure to causal agents, intervention in the organization of work (reduction of environmental stressors, reduction of the number of persons exposed and

of the time of exposure), and use of individual protective equipment (masks, filters and air supplies). Another form of prevention especially for patients known to be atopic, is immunotherapy, which helps control allergies and prevents recurrence.5,12

Since exposure to aerodispersoids may elicit the development of an inflammatory process, which in turn may be one of the possible etiologies of CRS, the objective of the present study was to determine the prevalence of CRS among workers exposed to cotton dust in order to classify rhinosinusitis as a possible occupational disease related to this irritant/allergen. An additional objective was to determine the possible association between responses to validated questionnaires and complementary exams for the diagnosis of CRS in this population.

Casuisitic and Methods

The present analytical, observational cross-sectional study was approved by the Ethics Committee of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo (protocol no. 10183/2009). The study was based on the application and analysis of two questionnaires applied to a total of 133 workers employed by “Cooperativa Nova Esperança” located in the city of Nova Odessa, State of São Paulo, Brazil. Questionnaire 1 (Annex 1) was used to screen for a diagnosis of CRS and Questionnaire 2 was the Sino-Nasal Outcome Test – 22 (SNOT-22) (Annex 2).

Questionnaire 1 (Annex), used for screening, contained questions about the presence or absence of symptoms that define a diagnosis of RS according to the European Position Paper on Rhinosinusitis and Nasal Polyposis (EPOS).2

SNOT-22 is a questionnaire adapted from SNOT-20; both of these instruments have been validated internationally and are easy to use in clinical practice to determine the impact of RS on the quality of life of the patient and can be used to measure the results of surgical intervention.14,15

The workers studied in the present investigation were those employed in Unit II of the above company, where all of them are exposed to cotton dust due to the physical characteristics of the unit. It should be pointed out that most of the workers studied are part of a cooperative, a fact that reduces the turnover of the sample and increases the

time of work in the company, i.e., the time of exposure to cotton dust, with a consequent reduction of previous exposure bias and causing time of exposure to be very importante for the health of each individual. The diagnostic suspicion of CRS was based solely on the clinical criteria proposed by the directives of EPOS.2

After an initial epidemiological screening in order to detect workers who fulfilled the clinical criteria for CRS, 47 subjects were invited to undergo complementary exams in order to confirm the clinical diagnosis. Thus, the 37 subjects who agreed to participate in this stage of the study were submitted to nasofibroscopy and to computed tomography of the paranasal sinuses (CTPN) performed by the same examiner on the same day.

Workers who were not exposed to cotton dust throughout the workday or who refused to answer the questionnaires were excluded from the study.

The study was approved by the Ethics Committee of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, and all patients gave written informed consent to participate.

Results

By analysis of the data collected during the initial epidemiological survey we determined the prevalence of clinical criteria suggestive of CRS among the workers exposed to cotton dust. A total of 133 workers (66.4% of them women and 33.6% men) replied to the questionnaires (Table 1).

Mean age was 39 years and mean time on the job was 11 years. Based on the screening performed with questionnaire 1 and of the EPOS directives for the diagnosis of RS, 35.3% (n = 47) of the subjects fulfilled the clinical criteria for a diagnosis of CRS (Table 2).

All 133 workers also replied to the SNOT-22 questionnaire, with a mean score of 28 points being obtained. All workers who fulfilled the clinical criteria for CRS (n = 47) were invited to undergo the two complementary exams, i.e., nasofibrolaryngoscopy and CTPN. Of these, only 33 accepted to undergo the procedures.

The subjects were divided into three groups to be compared regarding the SNOT -22 score: group 1, workers who fulfilled the clinical criteria for CRS and who

underwent the complementary exams (n = 37); group 2, workers who fulfilled the clinical criteria for CRS and who refused to undergo the complementary exams (n = 10); group 3, workers who did not fulfill the criteria for CRS (n = 86) (Table 3).

Comparative analysis of SNOT-22 scores revealed that groups 1 and 2 (which fulfilled the clinical criteria for CRS) had a significantly higher score than group 3 (subjects with no clinical signs of CRS) (Table 4).

Among the 37 workers who accepted to undergo the complementary exams for the diagnosis of CRS, nasofibrolaryngoscopy revealed changes compatible with CRS in 25 (67.6%) and CTPN provided a diagnostic confirmation in 26 (70.3%) (Tables 5 and 6). CTPN was considered to be positive when the Lund-Mackay score was higher than 0, and nasofibroscopy was considered to be positive when the Lund-Kennedy score was higher than 2.17,18

Discussion

Rhinosinusites are inflammations of the sinusal mucosa that can be considered to be of occupational origin when the job activity of affected individuals plays a contributing or additional role in their development, since the etiology is usually multicausal.2,3 Due to their nature, they may be of allergic origin or may be provoked by the inhalation of irritant or contaminant agents (viruses, bacteria and fungi). They may also affect one or more sinus cavities. 3,5,6

The nose and the paranasal cavities depend on the good functioning of mucociliary transport, which in turn requires the presence of ideal pH and temperature conditions in the nose and in the paranasal sinuses. Abrupt changes in temperature, inhalatory irritants, allergies or systemic diseases such as ciliary diskinesia may alter the mucociliary transport, predisposing an individual to bacterial infection. 11

The causal agentes of occupational origin most frequently mentioned in the literature are: chromium, zinc, nickel, cadmium, manganese, selenium and arsenic compounds used in the soldering and galvanization industry, for wood conservation and at other sites; fluorine, iodine, bromide and ammonia compounds used in the chemical, pharmaceutical, siderurgic, ceramic and fertilizer industry and others; cement, at times with the formation of nasal or sinusal rhinoliths; silica, foundries, mineration industries

and quarries; glass fiber; fumes emitted by the manufacture of rubber, plastic, oils, organic solvents, and acid or alkaline mists.4,7 According to the Guide of Otorhinolaryngologic Occupational Diseases,7 cotton dust is not cited as a causal agent of RS, but is only related to occupational rhinitis. However, the present study showed that there is an association between this irritant and the diagnosis of RS, although we cannot state that the condition is a consequence of the action of cotton dust as a direct irritant of the nasal mucosa or is due to the inflammatory process caused by occupational rhinitis.

A high prevalence of CRS is detected in the general population not exposed to aggravating factors. According to Kaliner et al, 3 CRS can be considered to be a public health problem affecting approximately 14% of the adult American population and some studies have reported that its prevalence has increased over the last few years.3 In Canada the prevalence is 3.4% among men and 5.7% among women, and in Korea the prevalence is 1.01%.2 These diferences are due to the fact that the diagnoses were made by different methods, with the first study using a standardized questionnaire, the second using a clinical diagnosis made by doctors, and the third a diagnosis made with the aid of nasofibrolaryngoscopy.2,13 In the present study, the prevalence of the clinical signs and symptoms of CRS was 35.3%, with a diagnostic confirmation based on complementary exams in more than 70% of the sample. This represented a 19.6% prevalence confirmed by diagnostic methods in the total population studied, corresponding to a higher incidence than any other detected in the literature in specific population studies with respect to this disease. An additional group of workers (group 2, n=10), if submitted to complementary tests, might have increased the prevalence observed.

The present study demonstrated that the diagnostic complementation with both nasofibroscopy and CTPN confirmed a high rate of CRS in the population initially screened (70.3%) according to the directives for diagnostic definition recommended by the European Position Paper on Rhinosinusitis and Nasal Polyposis (EPOS). On this basis, we may state that the method used for the initial screening of the workers proved to be effective in clinical practice.