Characterization and quantification of epilepsy patients with hospital episodes in Portugal: A multicenter retrospective study from Liga Portuguesa Contra a Epilepsia.

INTRODUCTION: Epilepsy affects around 50 million people worldwide and is associated with lower quality of life scores, an increased risk of premature death, and significant socio-economic implications. The lack of updated evidence on current epidemiology and patient characterization creates considerable uncertainty regarding the epilepsy burden in Portugal. The study aims to characterize and quantify the epilepsy patients who have been hospitalized, with medical or surgical procedures involved, and to analyze their associated comorbidities and mortality rates. METHODS: A multicenter retrospective study was conducted using hospital production data of epilepsy patients. The study included all patients diagnosed with epilepsy-related International Classification of Diseases-9/10 codes between 2015 and 2018 in 57 Portuguese National Health Service (NHS) hospitals (n = 57 institutions). Patient characterization and quantification were done for all patients with an epilepsy diagnosis, with specific analyses focusing on those whose primary diagnosis was epilepsy. Baseline, demographic, and clinical characteristics were analyzed using descriptive statistics. RESULTS: Between 2015 and 2018, a total of 80,494 hospital episodes (i.e., patient visit that generates hospitalization and procedures) were recorded, with 18 % to 19 % directly related to epilepsy. Among these epilepsy-related hospital episodes, 13.0 % led to short term hospitalizations (less than 24 h). Additionally, the average length of stay for all these epilepsy-related episodes was 8 days. A total of 49,481 patients were identified with epilepsy based on ICD-9/10 codes. The median age of patients was 64 years (min: 0; max: 104), with a distribution of 4.8 patients per 1,000 inhabitants. From the total of deaths (9,606) between 2015 and 2018, 14% were associated with patients whose primary diagnosis was epilepsy, with 545 of these being epilepsy-related deaths. Among patients with a primary diagnosis of epilepsy, the most common comorbidities were hypertension (24%) and psychiatric-related or similar comorbidities (15%), such as alcohol dependance, depressive and major depressive disorders, dementia and other convulsions. CONCLUSION: This study showed similar results to other European countries. However, due to methodological limitations, a prospective epidemiological study is needed to support this observation. Furthermore, the present study provides a comprehensive picture of hospitalized epilepsy patients in Portugal, their comorbidities, mortality, and hospital procedures.

Burden of Disease and Cost of Illness of Inflammatory Bowel Diseases in Portugal.

Background: Inflammatory bowel diseases' (IBD) increasing incidence and prevalence place a heavy health and economic burden on society. Objectives: This study assesses the burden and cost of IBD in Portugal to support the definition of health policies, resource allocation, and patient care. Methods: The burden of disease was expressed using disability-adjusted life years (DALY). Costs were estimated considering the societal perspective, using a prevalence-based model and prices established by law. An expert panel composed of 5 expert Portuguese gastroenterologists and a patient-reported study were conducted to support the cost analysis and fill in information gaps. Results: In Portugal, with a prevalence of 24,069 IBD patients and an incidence of 15/100,000, the burden of disease was estimated at 6,067 DALYs: 507 resulting from premature deaths and 5,560 from disability. Total cost was estimated at EUR 146 million per year, with direct costs representing 59%. Average yearly cost per IBD patient is EUR 6,075, where 60% is related to Crohn's disease and 40% to ulcerative colitis (UC). Conclusion: This study estimates the annual health burden and cost of IBD in Portugal, thus generating information with the intent to raise awareness of the need to advance health policies as well as better clinical and economic decisions in this pathology.

Contexto: A crescente incidência e prevalência das Doenças Inflamatórias Intestinais (DII) representam um pesado fardo para a saúde e economia na sociedade. Objetivos: Este estudo avalia o custo e a carga da DII em Portugal, com o objetivo de suportar a definição de políticas de saúde, alocação de recursos e cuidados com o doente. Métodos: A carga da doença foi calculada utilizando anos de vida ajustados à incapacidade (DALY). Os custos foram estimados tendo em conta a perspetiva da sociedade, utilizando um modelo baseado na prevalência e preços estabelecidos por lei. Foi realizado um painel de peritos, composto por 5 gastroenterologistas portugueses, assim como um estudo de mercado a doentes, de forma a suportar a análise de custos e colmatar lacunas de informação. Resultados: Em Portugal, com uma prevalência de 24,069 doentes e uma incidência de 15/100,000, o peso das DII foi estimado em 6.067 DALYs: 507 dos quais resultantes de mortes prematuras e 5.560 de incapacidade. O custo total foi estimado em 146 milhões de euros por ano, com os custos diretos a representarem 59% do total. O custo médio anual por doente de DII é de 6.075 EUR, onde 60% está relacionado com Doença de Crohn (DC) e 40% com Colite Ulcerosa. Conclusão: Este estudo estima os encargos anuais para a saúde e o custo da DII em Portugal, gerando informação relevante, com o intuito de alertar para a necessidade de uma evolução nas políticas de saúde, assim como como suportar melhores decisões clínicas e económicas nesta patologia.

Multiple Myeloma in Portugal: Burden of Disease and Cost of Illness.

BACKGROUND: Multiple myeloma (MM) is the second most common hematological cancer worldwide and has significant morbidity and mortality and is increasing in incidence. While MM management costs are considerable, specific economic data at the country level remain scarce. OBJECTIVE: This study assesses the burden and cost of MM in Portugal from the perspective of the National Health Service (NHS) to support the definition of health policies, resource allocation and patient care. METHODS: Developed by the Portuguese Multiple Myeloma Group, this study considers the most recent available data. Burden of disease was measured using disability-adjusted life-years (DALYs). The cost of MM was estimated using a prevalence-based model that estimated direct costs for the NHS considering all costs associated with diagnosis, hospitalizations, surgeries, emergency visits, medical appointments, drugs and transportation. Costs were quantified based on the diagnosis-related group funding price, except for drug usage, which was calculated using the average hospital product stock price. RESULTS: The burden of disease attributable to MM for 2018 was estimated at 8931 DALYs: 8570 resulting from premature deaths and 361 from disability. Average yearly direct costs per patients with MM amounted to €31,449 (year 2018 values). Total direct costs are estimated at €61 million per year. CONCLUSIONS: The mortality rate in MM means that most DALYs are due to years of life lost rather than years lost due to disability. This study generates comprehensive data on the burden and cost of MM in Portugal and provides updated insights into the costs associated with the management of MM.

Low-Pressure Hydrocephalus and Shunt Malfunction Following a Lumbar Puncture in an Adult Reversed by an Epidural Blood Patch.

BACKGROUND: Low-pressure hydrocephalus (LPH) is a relatively rare condition, and its presentation is similar to the classically seen high-pressure hydrocephalus, with headaches, cranial nerve dysfunction, ataxia, and disturbances of consciousness. Cerebral cerebrospinal fluid loss in the presence of altered brain viscoelastic properties has previously been suggested as the pathophysiologic process leading to ventriculomegaly, despite low or negative intracranial pressures and patent shunts. More recently, cerebral venous overdrainage has been proposed as a possible explanation in the pathogenesis of LPH, although its connection to lumbar punctures in patients with shunts has not been contemplated yet. The effectiveness of epidural blood patch in the management of post-lumbar puncture LPH has been shown in children but has not been reported in adults. CASE DESCRIPTION: Herein we detail 2 episodes of shunt malfunction in a 30-year-old female patient with a history of hydrocephalus related to a posterior fossa tumor diagnosed during childhood. In both instances, imaging studies demonstrated ventricular dilation along with perimedullary cistern enlargement and brainstem distortion, which occurred following a lumbar puncture despite a patent shunt. A lumbar blood patch was effective in both episodes, enabling resolution of the ventriculomegaly and a good outcome. CONCLUSIONS: A blood patch can be efficient in adults with post-lumbar puncture LPH. Some symptoms may be explained by brainstem compression caused by enlarged cerebrospinal fluid spaces at the skull base. The role of cerebral venous overdrainage in the setting of post-lumbar puncture LPH is further supported.

Severe Intracranial Hypotension After a Middle Fossa Approach for Spontaneous Otogenic Pneumocephalus.

BACKGROUND: Spontaneous otogenic pneumocephalus is a rare condition caused by erosion of the tegmen tympani with subsequent entrance of air into the intracranial space. Its pathogenesis is thought to involve a previous state of intracranial hypotension, which pulls air into the intracranial cavity. The surgical management involves obliteration of the tegmen defect via a mastoidectomy or a middle fossa approach. Lumbar drainage has been used safely as an adjunct to middle fossa approaches so as to provide brain relaxation and decrease the incidence of postoperative cerebrospinal fluid leaks. CASE DESCRIPTION: A 66-year-old male patient with otogenic pneumocephalus caused by nose blowing underwent repair of a tegmen tympani defect through a middle fossa approach, with the aid of intraoperative lumbar drainage. Progressive neurologic deterioration was seen postoperatively with obtundation and anisocoria. Computed tomography scans of the head demonstrated marked midline shift and transtentorial herniation. Recumbency and blood patch failed to improve the neurological condition. Intrathecal infusion of normal saline enabled clinical and radiological improvement. CONCLUSIONS: Intraoperative lumbar drainage during a middle fossa approach for spontaneous otogenic pneumocephalus may dramatically aggravate a state of preexisting intracranial hypotension and lead to transtentorial herniation.

Fluoroscopy only for the placement of long iliac screws: A study on 14 patients.

BACKGROUND: Iliac screw placement is challenging due to the particular anatomy of the ilium. Most series have reported the use of relatively short (≤90 mm in length) screws despite a long iliac buttress, which has an average length of 129 mm in females and 141 mm in males. This study describes a series of 14 patients who underwent placement of long iliac screws (≥100 mm in length) as part of a spinopelvic fusion utilizing fluoroscopy alone. METHODS: All patients who received at least one long iliac screw were included in this study. Placement accuracy, the average distance from the screw tip to the anterior inferior iliac spine (AIIS), neurovascular injuries, acetabulum and/or sciatic notch violations, and screw prominence were all measured. RESULTS: Fourteen patients received 38 iliac screws, with 31 screws being ≥100 mm in length. The accuracy rate was 87.1% (27/31) for the long iliac screws. The average shortest distance from the iliac screw tip to the AIIS was 15.5 mm for the right-sided and 17.1 mm for the left-sided ilia. There were no neurovascular injuries, acetabulum, or sciatic notch violations, and no screws loosened or fractured. Of interest, only one patient required off-set connectors to link the rods to the iliac screws. CONCLUSIONS: Placement of long iliac screws under intraoperative fluoroscopy only was shown to be feasible, with a high accuracy rate and few complications, in this series of patients.

Progressively Enlarging Cerebellar Hematoma Concurrent with T-DM1 Treatment.

BACKGROUND: Trastuzumab emtansine, an antibody-drug conjugate commonly abbreviated as T-DM1, is accepted as effective therapy for trastuzumab-resistant metastatic HER2-positive breast cancer. T-DM1 significantly increases progression-free and overall survival when compared with lapatinib plus capecitabine in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane. Among the common side effects related to T-DM1, thrombocytopenia and mucosal hemorrhage are seen, although they are infrequently judged to be clinically significant. Intracranial hemorrhages are extremely rare, and only 3 cases of hematomas have been reported in association with T-DM1 and remote radiotherapy, 2 of them with progressive enlargement. OBJECTIVE: Herein we describe a patient who presented with a cerebellar hematoma that progressively enlarged over 8 months during treatment with T-DM1 and only a few months after whole-brain radiation therapy plus a stereotactic radiosurgery boost for a HER2-positive breast cancer cerebellar metastasis. The pathology of the hematoma was similar to that in previous cases and suggested a unique pathophysiology related to an interaction between T-DMI and radiation therapy. CONCLUSIONS: A progressively enlarging intraparenchymal hematoma can be seen just a few months after delivery of radiation therapy for a metastatic brain lesion in HER2-positive breast cancer patients who are receiving T-DM1. In such patients, even a small focus of hemorrhage on magnetic resonance images should prompt close follow-up with serial imaging.

Matriderm for Management of Scalp Necrosis Following Surgical Treatment of Giant Parietal Encephalocele.

BACKGROUND: Management of encephaloceles is challenging when massive brain herniation is present. In such instances, an expansile cranioplasty may be attempted so as to preserve some herniated brain tissue. Complications such as wound dehiscence, cerebrospinal fluid leak, and scalp necrosis are postoperative concerns. The treatment of scalp necrosis with dural and brain exposure is certainly a challenge due to the complexity of flap techniques in such a young age. Herein we describe the use of a novel technique for the management of a scalp necrosis and dehiscence in an infant. CASE DESCRIPTION: A patient with a giant parietal encephalocele and massive brain herniation underwent an expansile cranioplasty. A large scalp necrosis ensued as a complication and later progressed to a suture dehiscence despite a new surgical intervention, with resultant brain exposure. A scalp reconstruction was subsequently performed using an artificial dermal substitute, laid directly onto the brain, followed by a split-thickness skin graft. We observed a rapid engraftment, without any further complications, with an acceptable cosmetic result in the long-term follow-up. CONCLUSION: A simple technique, such as the use of an artificial dermal matrix with simultaneous split-thickness skin graft, may be an effective treatment for the repair of scalp defects, even when coverage of exposed brain tissue is necessary, when no other techniques are found to be suitable.

Cerebellar cortical vein thrombosis mimicking a vermian tumor: case report.

Cortical vein thrombosis is an uncommon cause of stroke and generally occurs in the supratentorial compartment. Spontaneous venous thrombosis with infarction in the posterior fossa usually occurs in association with either dural sinus thrombosis and/or thrombosis of the petrosal vein, usually with venous infarction of the cerebellar hemisphere. Our goal is to present the case of a patient with thrombosis of cerebellar cortical veins, without sinus involvement, which mimicked a vermian cerebellar tumor.

Long iliac screw fixation in a case of isthmic spondyloptosis.

BACKGROUND: We report the case of a patient with a spondyloptosis who presented with progressive deformity and worsening neurological deficits. The patient had two previous lumbosacral instrumented fusions. CASE DESCRIPTION: A salvage revision surgery was performed, in which long iliac screws along with anterior column support at L5-S1 were used to immobilize the lumbosacral junction. Two years after the procedure a solid fusion is seen along with marked neurological improvement. CONCLUSIONS: Pelvic fixation using long iliac screws is a very useful technique that can be employed when revision surgery for high-grade spondylolisthesis is needed.

A Hemorrhagic Clival Chordoma with a Long Progression-Free Survival.

BACKGROUND: Chordomas and ecchordosis physaliphora may on rare occasions present with intracranial hemorrhage. Their distinction usually relies on the results of the Ki-67 proliferative index, with a result lower than 1% favoring ecchordosis physaliphora. Intracranial hemorrhagic chordomas have been linked to unfavorable prognosis, due to acute neurologic deterioration and death, or progression after treatment. To the best of our knowledge, this is the first report of a patient with an intracranial hemorrhagic chordoma who had a long progression-free survival. CASE DESCRIPTION: A 67-year-old woman presented with a large hemorrhagic clival tumor that was resected through an endonasal endoscopic approach. Physallipharous cells interspersed in a myxoid matrix, positivity for S-100, cytokeratin, and epithelial membrane antigen were found, along with an extremely low Ki-67 index. Imaging findings of bone erosion, a large size, and enhancement favored the diagnosis of chordoma. The patient received adjuvant stereotactic radiotherapy and has remained disease free after 4 years. CONCLUSIONS: Although hemorrhagic intracranial chordomas have been linked to unfavorable outcomes, our case demonstrates that they may have a low proliferative index, and a long progression-free survival may be seen.

Choroid plexus cauterization on treatment of hydranencephaly and maximal hydrocephalus.

INTRODUCTION: The standard treatment for hydranencephaly and maximal hydrocephalus consists of inserting shunts, although complications frequently occur. Choroid plexus cauterization (CPC) is an alternative, but its long-term efficacy and the factors associated with the success and failure of controlling head circumference (HC) are not well defined. OBJECTIVE: This study aims to evaluate the long-term efficacy and factors related to the success rate of CPC in the treatment of hydranencephaly and maximal hydrocephalus. METHOD: Forty-two children with maximal hydrocephalus and hydranencephaly underwent CPC from 2006 to 2014 and were retrospectively evaluated. Children with less than 3 months of follow-up were excluded. The long-term efficacy and success rate of possible variables (i.e., sex, type of malformation, type of surgery performed, treatment hospital, age, and HC at the time of surgery and birth) were evaluated. RESULTS: Thirty-four children were considered for the effectiveness analysis. Treatment was successful in 24 children (70.6%), and failure occurred in 10 children (29.4%). Failure was detected soon after the endoscopic procedure (average 116 days). There was no difference in effectiveness when comparing the age at the moment of surgery (p = 0.473), type of malformation (p = 1), HC at birth (0.699), and HC at the time of surgery (p = 0.648). The surgical death rate was 7.14%. CONCLUSION: Endoscopic CPC was a valid procedure used to treat hydranencephaly and maximal hydrocephaly, and it was effective in 70.6% of cases, with an average follow-up period of 32 months. When failures occurred, they occurred early. None of the analyzed variables interfered with the success of the treatment.

Pure Neuroendoscopic Resection of Cystic Cerebellar Tumors.

BACKGROUND: We describe the resection of cerebellar cystic tumors using pure neuroendoscopy. This technique consists of performing all of the procedures under an endoscopic view, with the instruments introduced into the operative field coaxially to the endoscope through a trocar. CASE DESCRIPTION: Three cases of cerebellar cystic lesions (two pilocytic astrocytomas and one hemangioblastoma) were approached using the pure neuroendoscopic technique. Under general anesthesia and prone positioning, a suboccipital burr hole was created. The endoscope was introduced into the tumor cavity, and a reddish nodule was identified. The monopolar electrode was used to coagulate and dissect the surrounding nodular tissue. Grasping forceps were used to remove the nodule. There were no complications related to tumor removal, and the patients recovered from their symptoms. The follow-up images showed reduction of the cavity with no contrast enhancement. CONCLUSION: The pure neuroendoscopic technique was shown to be minimally invasive and a successful and secure method to treat cystic cerebellar tumors.

Neuroendoscopic biopsy of brain lesions: accuracy and complications.

OBJECT: The authors conducted a study to analyze the accuracy of neuroendoscopic biopsies of ventricular and periventricular lesions and record any difficulties or complications of the neuroendoscopic biopsy procedure. METHODS: A total of 50 patients with different diseases consecutively underwent endoscopic biopsy procedures. The biopsy result was considered diagnostic if the pathologist reported any specific finding on which clinicians could base decisions about treatment or observation. The biopsy result was referred to as accurate if the results matched results of a sample obtained later or if the treatment response and disease evolution were compatible with the diagnosis. The biopsy result was considered inaccurate if results showed any relevant differences from those of the later sample or if the patient's disease did not evolve as expected. Complications were recorded and compared with those found in a literature review. RESULTS: For 2 patients, the procedure had to be terminated. The biopsy diagnostic rate was 89.6%, and the accuracy rate was 86%. Complications associated with the procedure were 3 hemorrhages (6%), 2 infections (4%), and 1 death (2%); no reoperations were needed. CONCLUSIONS: Endoscopic biopsy seems to be an accurate procedure with acceptable morbidity and mortality rates.

Dor de dente: percepção dos usuários da atenção básica de saúde / Pain of tooth: perception of users of basic health care

A dor é uma experiência privada e qualquer informação sobre ela provém daquele que sente. Esta pesquisa objetivou analisar a percepção dos usuários atendidos na Atenção Básica de Saúde no município de Campina Grande-PB, quanto à dor de dente. A pesquisa foi do tipo quanti-qualitativa, descritiva e transversal, sendo os dados coletados por entrevistas semi-estruturada. Dos 46 usuários entrevistados, 78% eram do sexo feminino e a faixa etária variou de 08 aos 57 anos. Cinquenta e seis por cento apresentavam renda de um salário e dedicação mais em atividades domésticas (46%) e certa equiparidade de nível escolar (básico, médio e fundamental). Os indivíduos demoram em média 60 dias para consultarem-se após dor de dente e mostraram-se em sua maioria ansiosos (27%). A maioria dos usuários (50%) só procura atendimento odontológico ao sentirem dor de dente e 59% optam pela extração dentária. A dor de dente leva o usuário a um grau de sofrimento que o obriga a utilizar terapias por vezes não recomendadas; interferindo no seu cotidiano. Embora não procure atendimento odontológico regularmente, quando o faz tem a finalidade pré-estabelecida de extração dentária. O rudimentar nível social contribui para esta mentalidade.

Pain is a private experience and any information on it comes from that feeling. The objective of our study was to examine the perceptions of users served in Primary Care Health in the city of Campina Grande-PB, as the toothache. The research was kind of quantitative and qualitative, descriptive and cross, and the data collected by semi-structured. Of the 46 users interviewed, 78% were female, the age ranged from 08 to 57 years. Fifty-six percent had an income of wage and more dedicated in domestic activities (46%) and had some equality-level school. They on average 60 days to consult one another after toothache. They were mostly anxious (27%). Thirty-nine percent no longer perform activities of daily life. Most users (50%) only seeking dental care after feeling toothache and 59% of them opting for dental extraction. The toothache takes the user to a degree of sufferring that requires the use therapies unexpected, it interferes with their daily lives. Although, not seek regular dental care and, when demand, designed to pre-established dental extraction. The rudimentary social level contributes to shis mentality.

Avaliação dos cirurgiões-dentistas sobre o gerenciamento dos resíduos odontológicos produzidos na prática diária / Evaluation of dentists regarding the management of dental waste produced in the daily routine

O gerenciamento dos resíduos dos serviços de saúde é um problema que exige a atenção das autoridades municipais e administrações dos mesmos por suas características inerentes. Exige manuseio, armazenamento, coleta, transporte e destinos específicos, devido ao fato dos resíduos, produzidos pelas instituições, muitas vezes induzirem enfermidades ou outros danos. Este estudo objetivou avaliar o gerenciamento dos resíduos odontológicos gerados por 85 consultórios odontológicos privados da cidade de Campina grande-PB...

Infecção por Rhodococcus equi em imunossuprimidos: uma revisão / Rhodococcus equi infection in human immunodeficiency: a review

O nocardioforme actinomiceto Rhodococcus equi é um importante patógeno de equinos e um patógeno emergente oportunista de humanos. Infecta, frequentemente, potroscom menos de 6 meses de idade. Amaioria dos humanos infectados apresenta algum deficit na imunidade celular e contato prévio com animais, solo contaminado ou ambos. A inalação dos organismos infectantes do solo pode levar a uma crônica e severa pneumonia piogranulomatosa em potros e pacientes imunocomprometidos. Alem disso, colite ulcerativa é uma sequela comum em potros e a disseminação do pulmão para outros sítios não é rara, tanto em animais quanto em humanos. Embora o R. equi, um cocobacilo gram-positivo e bactéria intracelular facultativa, seja susceptível à  morte por neutrófilos, ele é capaz de resistir as defesas macrofágicas inatas e estabelecer residência no ambiente intracelular desse fagócito. Usualmente, o pulmão é o órgão primário da infecção. As manifestações de disseminação extrapulmonares, fruto de bacteremia,têm sido descritas como abscessos cutâneo, cerebral, ósseo, etc. As manifestações clínicas da doença são febre, dispnéia, tosse, expectoração, dor torácica, hemoptise, emagrecimento, entre outras assim como na tuberculose. A propedêutica da rodococose inclui radiografia de tórax, exame direto e cultura do escarro, hemocultura, broncoscopia com BAL, biopsia transbrônquica, aspiração transparietal, exame anatomopatológico e, mais recentemente, análise genética. No diagnóstico diferencial da rodococose consideram-se tuberculose, nocardiose, actinomicose, abscesso pulmonar, pneumonia bacteriana por Pneumocystis carinii e outros...

The nocardioform actinomycete Rhodococcus equi is an important pathogen of horses and an emerging opportunistic pathogen of humans. The infection occurs most in foals with six months age. Most of the infected humans has some deficit in cellularimmunity and a previous contact with animals, contaminated soil or both. Inhalation of the soil-borne organism can lead to chronic and severe pyogranulomatous pneumonia in young horses and immunocompromised people. In addition, ulcerative colitis is a common sequel to infection in foals, and dissemination from the lung to other body sites is not uncommon in either horse or human. Although R. equi, a facultative intracellular bacterium, is susceptible to neutrophil-mediated killer, it is able to resist innate macrophage defenses and establish residencewithin the intracellular environment of thatphagocyte. Usually, the lung is the first organ to be compromised. The extra pulmonarymanifestations, resultant of the bloodspread bacteria, are cutaneous, bone and cerebral abscess. The clinical manifestations of the disease are fever, dyspnea, cough, increased sputum production, chest pain, hemoptysis,weight loss and others, like in tuberculosis. The investigation to diagnosis includes routine chest radiographs, sputum smears and cultures, hemoccult, bronchoscopy with BAL, over bronchioles biopsy, over parietal aspiration, pathologic analysis and more recently through genetic analysis...