Neumopatías intersticiales Profesor Titular: Dr. Enrique Díaz Greene Profesor Adjunto: Dr. Federico Rodríguez Weber Dr. Braulio Solano Estrada R2MI

Caso viñeta

Caso viñeta MAPFRE MEDICINA, 2001; vol. 12, n.° 3 Masculino de 52 años, fumador activo de 30 paquetes/ año, albañil. Refiere contacto con escayolas. Refiere dos años de evolución de astenia, artralgias y mialgias. Mes y medio previo al ingreso refiere incremento de la sensación de astenia, que se acompaña de tos no productiva, pérdida de 8 kg de peso, sudoración profusa y presencia de disnea a moderados esfuerzos. El examen físico no reveló datos de interés. Las pruebas de laboratorio demostraron: leucocitos 32,4 x 109/l (84% neutrófilos, 6% linfocitos, 4% monocitos). VSG 69 mm; PCR 118 mg/l. Gasometría arterial al aire ambiente: pH 7,42, pO2 66 mm Hg, pCO2 38 mm Hg.

Revisión

Generalidades Grupo heterogeneo de enfermedades King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Grupo heterogeneo de enfermedades Agrupadas juntas por compartir características Clínicas Radiográficas Fisiológicas patológicas El término intersticial no implica que sólo afecten a esta región anatómica

Generalidades Las causas identificables más comunes son King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Las causas identificables más comunes son Exposición a agentes ambientales Toxicidad a medicamentos Complicación de enfermedades del tejido conectivo Artrtitis reumatoide LES Polimiositis / Dermatomiositis Esclerodermia Schögren

Clasificación Causa conocida Causa desconocida ILD asociada a enfermedad de tejido conectivo (AR, polimiositis, esclerodermia) Neumonía por hipersensibilidad (pulmón de granjero, etc.) Neumoconiosis (asbestosis, silicosis, etc.) ILD inducida por fármacos (quimioterápicos, amiodarona, nitrofurantoína) ILD relacionadas al tabaquismo ILD inducida por radiación ILD inducida por inhalación de tóxicos (cocaína, cloruro de zinc, amonio) Causa desconocida Fibrosis pulmonar idiopática Sarcoidosis Otras neumonías intersticiales idiopáticas Neumonía organizada criptogénica Neumonía intersticial inespecífica Neumonía intersticial linfocítica Neumonía intersticial aguda Neumonías eosinofílicas Vasculitis pulmonar Linfangiomatosis pulmonar Proteinosis alveolar pulmonar Otras enfermedades raras

Causas de consulta por primera vez King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Disnea De esfuerzo Progresiva Tos Persistente No productiva Radiografía de tórax anormal Historia de exposición ocupacional Anormalidades en la espirometría

Antecedentes Historia clínica Antecedentes médicos Ocupacionales King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Historia clínica Antecedentes médicos Ocupacionales Factores de riesgo para VIH Edad Entre los 20 y 40 años Sarcoidosis, linfangioleiomiomatosis, histiocitosis, Enfermedad de Gaucher Mayores de 50 años Fibrosis pulmonar idiopática, ILD relacionada al tabaquismo

Antecedentes Género Mujeres premenopáusicas Hombres King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Género Mujeres premenopáusicas Linfangioleiomiomatosis Esclerosis tuberosa Hombres Es más frecuente su asociación a AR Neumoconiosis

Curso Procesos agudos y subagudos Curso crónico o asintomático King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Procesos agudos y subagudos Neumonía eosinofílica aguda Neumonía organizada criptogénica Relacionada a enfermedades del tejido conectivo Curso crónico o asintomático Fibrosis pulmonar idiopática Sarcoidosis Neumoconiosis Curso variable Neumonitis por hipersensibilidad sarcoidosis

Antecedentes médicos Enfermedades del tejido conectivo King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Enfermedades del tejido conectivo Enfermedad inflamatoria intestinal Cáncer (enfermedad per se, tratamiento) Amiodarona Rinitis alérgica / Asma Churg – Strauss VIH

Tabaquismo Aumento en la prevalencia King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Aumento en la prevalencia Histiocitosis de células de Langerhans Neumonitis intersticial descamativa Bronquiolitis respiratoria/enfermedad pulmonar intersticial Fibrosis pulmonar intersticial Enfermedades propias de no fumadores Sarcoidosis Neumonitis por hipersensibilidad

Radiación y medicamentos King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Daño relativo a la dosis de radiación Daño agudo (cuatro a doce semanas) Lesiones tardías (seis a doce meses) Relacionado a quimioterapia Adriamicina, etopósido, gemcitabina, paclitaxel

Exposición ambiental Listado cronológico King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Listado cronológico Empleo Vivienda Estilo de vida Exposición a polvos, gases, químicos

Cuadro clínico King Approach to the adult with interstitial lung disease: Clinical evaluation http://uptodate.com Revisión de mayo 2010 Disnea Curso insidioso, aumenta con el ejercicio Tos Generalmente es no productiva Hemoptisis Síndromes de hemorragia alveolar, linfangioleiomiomatosis, enfermedad pulmonar venooclusiva, vasculitis granulomatosa Sibilancias Carcinomatosis linfangítica, Churg-Strauss, neumonía eosinofílica crónica Dolor torácico Común en enfermedades del tejido conectivo Síntomas extrapulmonares Propios de enfermedades del tejido conectivo

Patologías específicas

Enfermedades Pulmonares Intersticiales Neumonías intersticiales Idiopáticas Fibrosis Pulmonar Idiopática (IPF) Neumonía Intersticial Inespecífica (NSIP) Neumonía Intersticial Descamativa (DIP) Bronquiolitis respiratoria (RB) Neumonía Intersticial Aguda (AIP) Neumonía Intersticial Linfoide (LIP) Neumonía Organizada Criptogénica (COP)

Fibrosis Pulmonar Idiopática Características Lóbulo inferior, predominancia subpleural Inflamación intersticial leve con fibrosis Cicatrización crónica con distorsión arquitectural y «panal de abeja» Key features include lower lobe and subpleural predominance, geographical and temporal heterogeneity, relatively mild interstitial inflammation with fibrosis, typically with normal or only mildly affected intervening lung.8 Ultimately this results in chronic scarring with architectural distortion and honeycombing. The distinctive fibroblastic focus, a hallmark lesion that is the site of active fibrosis, is not unique to UIP but is seen at the interface between dense peripheral fibrosis and more normal lung centrally in the lobule (Fig. 1). Ground glass opacification is seen, but seldom extensive

Fibrosis Pulmonar Idiopática PATOGÉNESIS «inflamatoria/alveolitis» Respuesta a estímulo desconocido Si no se trata  lesión pumonar progresiva y fibrosis «epitelial/mesenquimatosa» Múltiples episodios de activación de células epiteliales Daño inicial aún no es claro  disrupción del epitelio alveolar Migración, proliferación y activación de céls mesenquimatosas  focos fibroblásticos/miofibroblásticos  matriz extracelular excesiva The cause of IPF is unknown. Following Hamman and Rich’s description in 1944 of what we would now describe as AIP, the ‘inflammatory/alveolitis’’ hypothesis prevailed for several decades, the assumption being that IPF was a chronic inflammatory disease, occurring in response to an unknown stimulus, and if left untreated, led to progressive lung injury and ultimately fibrosis.10,11 As discussed later in this review, it is now clear that antiinflammatory agents have been disappointingly ineffective in the management of IPF The current ‘‘epithelial/mesenchymal’’ hypothesis suggests that IPF results from multiple episodes of epithelial cell activation from, as yet unidentified, exogenous and endogenous stimuli.14 The initial insult to the lungs is still unclear, and results in disruption of the alveolar epithelium Consequently, migration, proliferation and activation of mesenchymal cells occurs, resulting in the formation of fibroblastic/myofibroblastic foci (Fig. 1), with excessive accumulation of extra-cellular matrix, mirroring abnormal wound repair.14 The origin of the fibroblasts, key cells in the pathogenesis of IPF, is still unclear, and is possible that extrapulmonary, as well as pulmonary progenitor cells are involved in the aberrant repair/remodelling process.16–19 This complex process is well-described elsewhere and offers potential targets for therapeutic intervention.14

Fibrosis Pulmonar Idiopática Foco fibroblástico, no exclusivo de UIP, se observa en la interfaz entre fibrosis periférica densa y pulmón normal. The distinctive fibroblastic focus, a hallmark lesion that is the site of active fibrosis, is not unique to UIP but is seen at the interface between dense peripheral fibrosis and more normal lung centrally in the lobule (Fig. 1). Ground glass opacification is seen, but seldom extensive The photograph shows a large fibroblastic focus (arrow) in an area of interstitial chronic inflammation, located beneath epithelial cells that line the luminal surface (magnification 200).

Fibrosis Pulmonar Idiopática Epidemiología Más común en varones Incidencia M 11/7 F Prevalencia M 20/ 13 F Más común edad avanzada Edad pico 67-69 años Incremento en incidencia 11% anual entre 1991 y 2003  se duplica el núm de dx cada 8 años. In one of the best population-based studies, from Bernalillo County in New Mexico, Coultas et al.21 recorded all new cases of interstitial lung disease registered over a 2-year period in a population of nearly half a million inhabitants. Coultas et al.21 reported an incidence/prevalence (male/female) per 105 population of 11/7 and 20/13, respectively. A Norwegian study reported an incidence/prevalence for hospitalised IPF of 4.3 and 20 per 1000 000.22 In the UK, data has been analysed from a primary care database of approximately 4 million patients, with 962 cases of IPF identified between 1991 and 2003, excluding patients with connective tissue diseases and adjusting for age and gender.4 The incidence of IPF has been reported as rising by 11% annually between 1991 and 2003, suggesting the number of recorded diagnoses of IPF is doubling every 8 years.4

Fibrosis Pulmonar Idiopática Factores de riesgo Tabaquismo Fármacos (antidepresivos) Aspiración crónica Reflujo gastroesofágico mayor prevalencia, frecuentemente clínicamente oculto Polvo metal y madera Agentes infecciosos HVC, EBV Many potential risk factors have been suggested as being linked with IPF,7 notably cigarette smoking,25 medication (anti-depressants),26 chronic aspiration, 27–29 metal and wood dusts 24,30,31 and infectious agents.7,20,21 Viral infections suggested to be linked with IPF include hepatitis C, adenovirus and Epstein– Barr virus.32 In vivo, Epstein–Barr replication has been reported to be significantly increased within type II alveolar epithelial cells in lung biopsies from patients with IPF, compared to controls.33 Several studies have suggested that IPF may be related to repeated aspiration of gastric contents over long periods of time and a recent study suggests that abnormal gastro-oesophageal reflux is highly prevalent, but often clinically occult, in patients with IPF.

Fibrosis Pulmonar Idiopática Familiar – rara UK 1.34 casos por millón 0.5 - 2.2% de los casos Finlandia 3.3 – 3.7% Heterogeneidad fenotípica en la mayoría de las familias Genes: antagonista del receptor de IL-1 TNF-a y receptor de complemento 1 Proteína C de surfactante Familial IPF is rare, with a recent UK study reporting a prevalence of 1.34 cases per million, accounting for only 0.5–2.2% of all cases.34 A Finnish study reported similar findings, with familial IPF accounting for 3.3–3.7% of cases.35 Clustering within families has been widely reported, and a group of 111 families, with 309 affected individuals, has recently been described36 Interestingly, phenotypic heterogeneity was seen in almost half the families, with several subtypes of IIP reported Associations between IPF and specific polymorphisms in genes encoding interleukin-1 receptor antagonist, tumour necrosis factor-a and complement receptor 1 have been reported.37 Furthermore, two mutations in the gene encoding surfactant protein C have been identified, resulting in protein misfolding, causing type II epithelial cell injury.38,39 Susceptibility to IPF probably involves a combination of genetic polymorphisms related to epithelial cell injury and abnormal wound healing

Fibrosis Pulmonar Idiopática Fig. 10. UIP. (A) Chest radiograph shows ground-glass opacity, reticular abnormality, and loss of volume in both lower lungs. (B) Honeycombing (arrows), ground-glass attenuation, and reticular abnormality are seen in the same area on HRCT. This appearance corresponds to pathologic temporal heterogeneity. (C) Photomicrograph has a heterogeneous appearance at low magnification, with alternating areas of normal lung, interstitial inflammation, fibrosis, and honeycombing change (‘‘spatial and temporal heterogeneity’’) (hemotoxiline-eosine, original magnification 10).

Fibrosis Pulmonar Idiopática Criterios mayores (4 de 4) Exclusión de otras causas conocidas de enfermedad pulmonar intersticial, toxicidad por fármacos, exposición ambiental y colagenopatías Pruebas de función pulmonar anormales con evidencia de restricción con o sin intercambio gaseoso alterado Anormalidades reticulares bibasales con mínimas opacidades en vidrio despulido en HRCT Biopsia pulmonar transbronquial o lavado bronquioloalveolar que no muestre características de otro diagnóstico Criterios menores (3 de 4) Edad >50 años Inicio insidioso de disnea de esfuerzo sin otra explicación Duración de la enfermedad de 3 meses Estertores inspiratorios (secos o «velcro»)

Enfermedades Pulmonares Intersticiales Neumonías intersticiales Idiopáticas Fibrosis Pulmonar Idiopática (IPF) Neumonía Intersticial Inespecífica (NSIP) Neumonía Intersticial Descamativa (DIP) Bronquiolitis respiratoria (RB) Neumonía Intersticial Aguda (AIP) Neumonía Intersticial Linfoide (LIP) Neumonía Organizada Criptogénica (COP)

Neumonía Organizada Criptogénica Focos de neumonía organizada Davison 1983 – neumonía organizada sin enfermedad asociada identificable Epler et al, 1985 – neumonía organizada bronquiolitis obliterante Proliferación de tejido de granulación en espacios alveolares y en ocasiones en bronquiolos Foci of organizing pneumonia are commonly found at surgical lung biopsy in many settings (e.g., postinfectious, malignancy, drug-related lung injury, connective tissue disease–related, posttransplant, aspiration, inflammatory bowel disease), and even associated with other IIPs, including UIP. However, in 1983, Davison and coworkers (66) described a clinicopathologic entity of isolated organizing pneumonia in patients without an identifiable associated disease. In 1985, Epler and colleagues (67) described the same entity under the term bronchiolitis obliterans organizing pneumonia, and that latter term came into common usage. The ATS/ERS consensus statement recommended that the term cryptogenic organizing pneumonitis be used because it conveys the essential features of the syndrome described below and avoids confusion with airway diseases such as constrictive bronchiolitis obliterans proliferation of granulation tissue in alveolar spaces and sometimes bronchioles. It has also been known as idiopathic bronchiolitis obliterans organising pneumonia (BOOP), a term which does not reflect the true histopathological pattern of organising pneumonia. BOOP is not a recommended terminology to be used for COP as bronchioles are not always involved and it can easily be confused with obliterative bronchiolitis (OB), which is a completely different disease.

Neumonía Organizada Criptogénica Todas las edades, media de 50 años Sin predominio M : F Cuadro clínico Disnea de corta duración con tos seca o productiva Fiebre, sudoración, pérdida de peso y mialgia Laboratorio Neutrofilia en sangre periférica PCR y VSG elevadas COP usually presents with relatively short duration of dyspnea with dry or productive cough. Patients may have fever, sweats, weight loss and myalgia, and laboratory tests typically show increased CRP (C reactive protein), ESR (erythrocyte sedimentation rate) and peripheral blood neutrophilia.25 The presenting features are often indistinguishable from lung infection, so patients are frequently treated with multiple courses of antibiotics, and the diagnosis of COP is raised when the pneumonia fails to resolve, or when it relapses.

Neumonía Organizada Criptogénica NOC típico Buen pronóstico, remisión en 50% NOC fulminante agudo Características de SDRA Frecuentemente requiere VMA Ocasionalmente fatal sin progresar a fibrosis franca Biopsia: neumonía organizada NOC fibrosante Pronóstico variable Fibrosis intersticial leve no progresiva Algunos casos pueden llevar a progresión rápida de insuficiencia respiratoria COP can be subdivided into three variants according to prognosis. Typical COP is associated with good overall prognosis with spontaneous remission in about 50% of cases in most case series.26–29 Acute fulminant COP presents with features of acute respiratory distress syndrome (ARDS) and frequently needs mechanical ventilatory support. This rare variant is occasionally fatal without progressing to overt fibrosis. The biopsy shows features typical of organising pneumonia. It might pose a challenge to distinguish it from acute interstitial pneumonia on clinical and radiological grounds. Fibrosing COP is a rare subset of COP where clinical outcome is variable. There is usually mild interstitial fibrosis which is non-progressive in nature. Moreover there is evidence that some cases might lead to rapid progression of respiratory failure and death as described by case series of 10 patients by Cohen and colleagues

Neumonía Organizada Criptogénica Fig. 3. COP. (A) Chest radiograph shows consolidation in the right lower lung. Ground-glass opacity is seen in right upper and left middle lung. (B) An area of airspace consolidation is seen in right lower lobe on HRCT. Ground-glass attenuation is present in the left lung. (C) Photomicrograph from the area of airspace consolidation shows diffuse intraluminal organizing pneumonia (hemotoxiline-eosine, original magnification 10). CT scan (Fig. 4b) typically shows areas of airspace consolidation31,32 with air bronchograms. The distribution of parenchymal abnormality is usually peribronchial or subpleural with propensity to involve basal zones of the lung. There may be ground glass attenuation present in approximately 60% of cases with COP

Neumonía Organizada Criptogénica Tratamiento Esteroides (>80% responde) 0.5-1.9mg/kg/día inicialmente, a dosis de reducción por al menos 6 meses. Cursos más cortos se asocian a mayor recurrencia Pequeño porcentaje enfermedad progresiva a pesar de tx Ciclofosfamida – pocos datos muestran beneficio Pronóstico Excelente Supervivencia a 5 años cerca de 100% Although a small percentage of patients with COP improve spontaneously, corticosteroids are the mainstay of therapy. Treatment is usually given at high doses (0.5–1.0 mg/kg/day initially, then tapered) for at least 6 months. Shorter courses of therapy are associated with a high rate of recurrent disease. The vast majority (>80%) of patients will respond to corticosteroid treatment. A small percentage of patients will have progressive disease despite therapy. Alternative agents such as cyclophosphamide have been used but few data support any benefit. Although patients usually show signs of improvement within days of starting treatment, it is recommended that treatment with tapering doses of corticosteroids be given for 6 months or longer. Prognosis Survival in patients with COP is excellent, with 5-year survival estimated at close to 100%. An occasional case of COP may progress to respiratory failure and death. This usually occurs when the diagnosis and subsequent treatment are delayed.

Enfermedades Pulmonares Intersticiales Enfermedades Ambientales y Ocupacionales Neumoconiosis: asbestosis, silicosis Alveolitis Alérgica Extrínseca (EAA) Enfermedades Multisistémicas

Alveolitis Alérgica Extrínseca Neumonitis por hipersensibilidad Grupo de enfermedades pulmonares mediadas inmunológicamente en las que la inhalación repetida de ciertos antígenos (principalmente partículas orgánicas o químicos de bajo peso molecular) provoca una reacción de hipersensibilidad con inflamación granulomatosa en los bronquiolos distales y alvéolos de individuos susceptibles. The essence of this disease is an interacción between an external antigen and the host9s immune system. It must be clearly distinguished from a number of nonallergic, inflammatory reactions, such as "inhalation fevers", toxic alveolitis and organic dust toxic syndrome, which are also associated with the inhalation of organic dusts [2–4]. These reactions typically occur after a single exposure to an unusually high level of organic dust, and they may occur in "naı¨ve" subjects without previous exposure. In such toxic reactions, individual susceptibility is less apparent and all subjects that have the same degree of exposure develop a similar clinical illness. In contrast, individual susceptibility is a characteristic feature of an immune-mediated disease such as HP, such that only a small percentage of those exposed to the antigen develop the disease.

Alveolitis Alérgica Extrínseca Neumonitis por hipersensibilidad Grupo de enfermedades pulmonares mediadas inmunológicamente en las que la inhalación repetida de ciertos antígenos (principalmente partículas orgánicas o químicos de bajo peso molecular) provoca una reacción de hipersensibilidad con inflamación granulomatosa en los bronquiolos distales y alvéolos de individuos susceptibles. The essence of this disease is an interacción between an external antigen and the host9s immune system. It must be clearly distinguished from a number of nonallergic, inflammatory reactions, such as "inhalation fevers", toxic alveolitis and organic dust toxic syndrome, which are also associated with the inhalation of organic dusts [2–4]. These reactions typically occur after a single exposure to an unusually high level of organic dust, and they may occur in "naı¨ve" subjects without previous exposure. In such toxic reactions, individual susceptibility is less apparent and all subjects that have the same degree of exposure develop a similar clinical illness. In contrast, individual susceptibility is a characteristic feature of an immune-mediated disease such as HP, such that only a small percentage of those exposed to the antigen develop the disease.

Alveolitis Alérgica Extrínseca Sólo 5-15% de los sujetos expuestos a Ag provocador desarrollan la enfermedad 3.4% de criadores de pericos australianos 8% de criadores de palomas 4.3% de granjeros Un número mayor de sujetos expuestos al Ag desarrollan sensibilización (respuesta humoral o celular) pero no progresan a enfermedad. A characteristic feature of HP is that only 5–15% of subjects exposed to a provoking antigen develop the disease [48]. For example, y3.4% of budgerigar fanciers, 8% of pigeon fanciers, and 4.3% of farmers develop HP [21, 28, 39]. A much larger number of subjects exposed to the antigen develop sensitization in the form of a humoral or cellular immune response, but do not progress from sensitization to overt disease.

Alveolitis Alérgica Extrínseca Episodios recurrentes de disnea y tos, con fiebre, escalofríos y mal estado general Ocurre 4-8h después de la exposición, se resuelve usualmente dentro de 24 - 48h. PFR: Defecto restrictivo, difusión disminuida e hipoxemia RxTx: opacidad alveolar RESPUESTA MACRÓFAGO-LINFOCITARIA Forma Aguda Desarrollo insidioso de disnea, episodios discretos de síntomas agudos posterior a exposición al Ag FORMACIÓN DE GRANULOMAS Forma Subaguda Desarrollo insidioso de disnea FIBROSIS PULMONAR Forma crónica The acute form manifests as recurrent episodes of dyspnoea and cough with fever, chills and malaise occurring about 4–8 h after exposure to antigen, and usually resolving within about 24–48 h. Lung function tests typically show a restrictive defect with reduced gas diffusion and hypoxaemia, and a chest radiograph may show alveolar shadowing. The chronic form is characterized by the insidious development of dyspnoea and pulmonary fibrosis in a patient that has not experienced acute symptoms. The subacute form is similar to the chronic form in that dyspnoea develops insidiously, but these patients also have discrete episodes of acute symptoms after antigen exposure. Eur Respir J 2001; 18: Suppl. 32, 81s–92s

Alveolitis Alérgica Extrínseca Laboratorio Inespecífico: Leucocitosis, PCR elevada, Igs elevadas, complemento normal Ac precipitantes en el suero (Precipitinas IgG específicas para Ag) Si son negativas no excluyen dx Pruebas cutáneas: vía intradérmica con suero de ave, heno, etc al 1/100 (0.1mg/ml)  Pápula de 5mm  10mm positiva Inmediata (15min) más sensible y específica Semirretardada 4-8h Retardada 72h Baja especificidad Pruebas de provocación

Alveolitis Alérgica Extrínseca Tratamiento Suspender Exposición Antigen avoidance is the key element in the treatment of HP and complete cessation of exposure to the provoking antigen is the safest advice for these patients. In some circumstances, the recognition of a clinical syndrome can lead to changes in the occupational environment, so that the risk to workers is eliminated, as has occurred with sugar cane after the discovery of bagassosis [37]. Education of certain "at risk" populations may be helpful in the early recognition of symptoms and in encouraging them to adopt preventative strategies. Patients are sometimes reluctant to consult doctors when they fear that their livelihood is at stake, as in the case of farmers, or that their commitment to their sport will not be adequately appreciated, as in the case of pigeon fanciers. In order to gain the confidence of the patient, it is essential that the doctor is well informed about the different outcomes of the various forms of HP and has a sympathetic attitude to the difficulties a patient may have in achieving complete cessation of antigen exposure [91]. Patients with the acute progressive form of the disease have debilitating symptoms such that they are usually prepared to cease all exposure to the antigen once the diagnosis has been established

Distribución Sarcoidosis, Histiocitosis de Langerhans Silicosis, Fibrosis por carmustina Distribution Upper lung predominance: sarcoidosis, pulmonary Langerhans cell histiocytosis, silicosis, coal worker’s pneumoconiosis, carmustine-related pulmonary fibrosis (also consider tuberculosis, Pneumocystis pneumonia) Lower lung predominance: IPF, connective tissue disease–associated ILD, asbestosis (also consider chronic aspiration) Central predominance: sarcoidosis, berylliosis, pulmonary alveolar proteinosis Peripheral predominance: IPF, nonspecific interstitial pneumonia, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia (also consider pulmonary infarctions, septic pulmonary embolism)

Distribución Distribution Upper lung predominance: sarcoidosis, pulmonary Langerhans cell histiocytosis, silicosis, coal worker’s pneumoconiosis, carmustine-related pulmonary fibrosis (also consider tuberculosis, Pneumocystis pneumonia) Lower lung predominance: IPF, connective tissue disease–associated ILD, asbestosis (also consider chronic aspiration) Central predominance: sarcoidosis, berylliosis, pulmonary alveolar proteinosis Peripheral predominance: IPF, nonspecific interstitial pneumonia, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia (also consider pulmonary infarctions, septic pulmonary embolism) ILD asociada a enf de tejido conectivo, asbestosis, aspiración crónica

Distribución Sarcoidosis, beriliosis, proteinosis alveolar Distribution Upper lung predominance: sarcoidosis, pulmonary Langerhans cell histiocytosis, silicosis, coal worker’s pneumoconiosis, carmustine-related pulmonary fibrosis (also consider tuberculosis, Pneumocystis pneumonia) Lower lung predominance: IPF, connective tissue disease–associated ILD, asbestosis (also consider chronic aspiration) Central predominance: sarcoidosis, berylliosis, pulmonary alveolar proteinosis Peripheral predominance: IPF, nonspecific interstitial pneumonia, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia (also consider pulmonary infarctions, septic pulmonary embolism)

Distribución IFP, neumonía intersticial inespecífica, neumonía eosinofílica crónica, COP Distribution Upper lung predominance: sarcoidosis, pulmonary Langerhans cell histiocytosis, silicosis, coal worker’s pneumoconiosis, carmustine-related pulmonary fibrosis (also consider tuberculosis, Pneumocystis pneumonia) Lower lung predominance: IPF, connective tissue disease–associated ILD, asbestosis (also consider chronic aspiration) Central predominance: sarcoidosis, berylliosis, pulmonary alveolar proteinosis Peripheral predominance: IPF, nonspecific interstitial pneumonia, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia (also consider pulmonary infarctions, septic pulmonary embolism)

Valor diagnóstico de BAL en ILD Infecciones oportunistas: P jirovecii, hongos y Tb Hemorragia alveolar: macrófagos con hemosiderina Proteinosis alveolar pulmonar: macrófagos epumosos, sustancia PAS-positiva no celular lechosa Neumonía eosinofílica: eosinofilia >25% Asbestosis: cuerpos de asbesto Aspiración de lípidos: vacuolas citoplasmáticas de lípidos dentro de macrófagos alveolares Microlitiasis: cuerpos cálcicos

Elección de biopsia Transbronquial Abierta o videotoracoscopía Sarcoidosis Beriliosis Neumonía eosinofìlica Neumonía organizada Proteinosis alveolar Abierta o videotoracoscopía Granulomatosis de cels de Langerhans Linfangioleiomiomatosis Neumonía intersticial idiopática Granulomatosis de Wegener

Caso viñeta

Caso Clínico Todos los estudios bacteriológicos en sangre, esputo, broncoaspirado y lavado broncoalveolar (LBA) fueron negativos. Exploración funcional respiratoria: FVC 2.760 ml (75%), FEVI 2.080 ml (75%), FEV1/VC 70%, TLC 5.120 ml (95%), TLCO 16,2 (66%), TLCO/VA 13,2 (71%) Recuento citológico del LBA: linfocitos 19% (CD3 91%, CD4 41%, CD8 52%, cociente CD4/CD8 0,79), neutrófilos 21%, eosinófilos 6%, células cebadas 3%. Biopsia transbronquial: múltiples acúmulos de macrófagos en espacios alveolares, reacción tipo neumonitis intersticial. MAPFRE MEDICINA, 2001; vol. 12, n.° 3

Caso Clínico El estudio de las precipitinas frente a los antígenos más comunes causantes de AAE fue negativo. El test cutáneo frente al estracto de esparto (1/100) fue positivo, con una pápula de 30 mm a los 15 minutos y de 15 mm a las 6 horas. En el cultivo del esparto aportado por el paciente se observó crecimiento de Aspergillus sp. y Sepedonium sp. Una semana de ingreso en la que el paciente no recibió ningún tipo de tratamiento, se objetivó mejoría radiológica con normalización de parámetros analíticos (recuento leucocitario, VSG, PCR). No se realizó test de provocación bronquial específica ante la negativa del paciente. Siete meses después de finalizado el contacto con el esparto, el paciente se encontraba asintomático y con un HRCT sin evidencia de patología pulmonar. MAPFRE MEDICINA, 2001; vol. 12, n.° 3

El esparto (Stipa tenacissima y Ligeum spartum) es una planta silvestre perteneciente al género de las gramíneas, que, tras un proceso de transformación, es utilizado para diversos fines industriales. Su uso como material de sostén en el interior de las escayolas es uno de ellos. Entre los trabajadores que lo manipulan se han descrito tres tipos de cuadros clínicos respiratorios: asma bronquial, enfermedad pulmonar obstructiva crónica y fibrosis, sin embargo no fue hasta 1984 cuando se describió el primer caso de alveolitis alérgica extrínseca secundaria al manejo de este material. El cuadro clínico suele ser, en general, semejante al del resto de las AAE, aunque a diferencia del resto se produce con igual frecuencia en individuos fumadores y no fumadores MAPFRE MEDICINA, 2001; vol. 12, n.° 3