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About 20% of DIPNECH patients are symptom free at the time they first present. The most common symptoms include:
- Chronic cough
- Shortness of breath or dyspnea when exercising or exerting one’s self
- Wheezing (less frequent)
- Hemoptysis (Infrequent)
Symptoms may be present for many years prior to diagnosis and are often ascribed to other lung conditions. Erroneous initial diagnoses of asthma or chronic obstructive pulmonary disease often are made in patients with DIPNECH.
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a diffuse parenchymal lung disease which often presents with symptoms of cough and shortness of breath. The pathological definition published by the World Health Organization is “a generalized proliferation of scattered single cells, small nodules (neuroendocrine bodies), or linear proliferations of pulmonary neuroendocrine (PNE) cells that may be confined to the bronchial and bronchiolar epithelium.” The true prevalence of this disease is not known. To date, just under 200 cases have been reported in the literature. However, with an increase in recognition of this disease by radiologists and pulmonologists, the number of cases has been increasing. DIPNECH predominantly affects middle-aged women with slowly progressive lung obstruction. DIPNECH is usually discovered in one of two ways: 1) as an unexpected finding following a lung surgery; or 2) by evaluation of a patient in a pulmonary clinic with longstanding, unexplained symptoms.
Tumor-like disorders of the lung pleura are a group of conditions that on initial radiological studies might be confused with malignant lesions. Radiologists must be aware of these conditions in order to avoid misdiagnosing patients. Examples of such lesions are: pleural plaques, thoracic splenosis, catamenial pneumothorax, pleural pseudotumor, diffuse pleural thickening, diffuse pulmonary lymphangiomatosis and Erdheim-Chester Disease.
Exposure to asbestos fibers reach the pleura of the lungs through the lymphatic channels or blood stream. Historically, ship builders and insulation workers are at greater risk.
Affected persons are usually asymptomatic.
On radiological studies, pleural plaques are visualized using conventional chest x-rays and computed tomography scans (CT scans). The locations of the lesions are mostly in the parietal pleura of the lungs, especially in the posterior/lateral regions of the thorax, diaphragmatic domes, and lung fissures. In some cases, calcifications are also evident, especially with CT scans.
No treatment is required since pleural plaques are benign. However, studies have demonstrated that pleural plaques are an independent risk factor for developing bronchogenic carcinoma and/or mesothelioma.
Alveolar disease is visible on chest radiography as small, ill-defined nodules of homogeneous density centered on the acini or bronchioles. The nodules coalesce early in the course of disease, such that the nodules may only be seen as soft fluffy edges in the periphery.
When the nodules are centered on the hilar regions, the chest x-ray may develop what is called the "butterfly," or "batwing" appearance. The nodules may also have a segmental or lobar distribution. Air alveolograms and air bronchograms can also be seen.
These findings appear soon after the onset of symptoms and change rapidly thereafter.
A segmental or lobar pattern may be apparent after aspiration pneumonia, atelectasis, lung contusion, localized pulmonary edema, obstructive pneumonia, pneumonia, pulmonary embolism with infarction, or tuberculosis.
Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, perivascular and perilymphatic tissues. It may occur when an injury to the lungs triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair damage. But in interstitial lung disease, the repair process goes awry and the tissue around the air sacs (alveoli) becomes scarred and thickened. This makes it more difficult for oxygen to pass into the bloodstream. The term ILD is used to distinguish these diseases from obstructive airways diseases.
In children, several unique forms of ILD exist which are specific for the young age groups. The acronym chILD is used for this group of diseases and is derived from the English name, Children’s Interstitial Lung Diseases – chILD.
Prolonged ILD may result in pulmonary fibrosis, but this is not always the case. Idiopathic pulmonary fibrosis is interstitial lung disease for which no obvious cause can be identified (idiopathic), and is associated with typical findings both radiographic (basal and pleural based fibrosis with honeycombing) and pathologic (temporally and spatially heterogeneous fibrosis, histopathologic honeycombing and fibroblastic foci).
In 2013 interstitial lung disease affected 595,000 people globally. This resulted in 471,000 deaths.
Alveolar lung diseases, are a group of diseases that mainly affect the alveoli of the lungs.
Pulmonary edema, connective tissue diseases, asbestosis, lymphangitic carcinomatosis, lymphoma, lymphangioleiomyomatosis, drug-induced lung diseases
- Lymphadenopathy
Sarcoidosis, silicosis, berylliosis, lymphangitic carcinomatosis, lymphoma, lymphocytic interstitial pneumonia
Most common:
- Chest Pain
- Cough
- Fever
- Shortness of breath
- Joint pain, stiffness, swelling
- Skin nodules
People may not present with all these symptoms or non at all.
From most to lest common:
- Pleural involvement (pleurisy, effusions)
- Pulmonary parenchymal nodules, more common in men than in women
- Rheumatoid-associated interstitial lung disease
- Bronchiolitis obliterans organizing pneumonia
- Obliterative bronchiolitis (obstructive lung disease/bronchiectasis)
- Rheumatoid-associated pulmonary hypertension
- Pulmonary vasculitis/arteritis
- Shrinking lung syndrome
- Miscellaneous: MTX, cricoarytenoid arthritis, infection, cancer
Symptoms of DPB include chronic sinusitis (inflamed paranasal sinuses), wheezing, crackles (respiratory sounds made by obstructions such as phlegm and secretions in the lungs), dyspnea (shortness of breath), and a severe cough that yields large amounts of sputum (coughed-up phlegm). There may be pus in the sputum, and affected individuals may have fever. Typical signs of DPB progression include (enlargement) of the bronchiolar passages and hypoxemia (low levels of oxygen in the blood). If DPB is left untreated, bronchiectasis will occur; it is characterized by dilation and thickening of the walls of the bronchioles, inflammatory damage to respiratory and terminal bronchioles, and pooling of mucus in the lungs. DPB is associated with progressive respiratory failure, hypercapnia (increased levels of carbon dioxide in the blood), and can eventually lead to pulmonary hypertension (high blood pressure in the pulmonary vein and artery) and cor pulmonale (dilation of the right ventricle of the heart, or "right heart failure").
The classic presentation of COP is the development of nonspecific systemic (e.g., fevers, chills, night sweats, fatigue, weight loss) and respiratory (e.g. difficulty breathing, cough) symptoms in association with filling of the lung alveoli that is visible on chest x-ray. This presentation is usually so suggestive of an infection that the majority of patients with COP have been treated with at least one failed course of antibiotics by the time the true diagnosis is made.
"Organizing" refers to unresolved pneumonia (in which the alveolar exudate persists and eventually undergoes fibrosis) in which fibrous tissue forms in the alveoli. The phase of resolution and/or remodeling following bacterial infections is commonly referred to as organizing pneumonia, both clinically and pathologically.
The term "bronchiolitis" generally refers to inflammation of the bronchioles. DPB is classified as a form of "primary bronchiolitis", which means that the underlying cause of bronchiolitis is originating from or is confined to the bronchioles. Along with DPB, additional forms of primary bronchiolitis include bronchiolitis obliterans, follicular bronchiolitis, respiratory bronchiolitis, mineral dust airway disease, and a number of others. Unlike DPB, bronchiolitis that is not considered "primary" would be associated with diseases of the larger airways, such as chronic bronchitis.
Pulmonary neuroendocrine tumors are neuroendocrine tumors localized to the lung: bronchus or pulmonary parenchyma.
Pulmonary neuroendocrine tumors include a spectrum of tumors from the low-grade typical pulmonary carcinoid tumor and intermediate-grade atypical pulmonary carcinoid tumor to the high-grade pulmonary large cell neuroendocrine carcinoma (LCNEC) and pulmonary small cell carcinoma (SCLC), with significant clinical, epidemiologic and genetic differences.
A pulmonary hematoma is a collection of blood within the tissue of the lung. It may result when a pulmonary laceration fills with blood. A lung laceration filled with air is called a pneumatocele. In some cases, both pneumatoceles and hematomas exist in the same injured lung. Pulmonary hematomas take longer to heal than simple pneumatoceles and commonly leave the lungs scarred. A pulmonary contusion is another cause of bleeding within the lung tissue, but these result from microhemorrhages, multiple small bleeds, and the bleeding is not a discrete mass but rather occurs within the lung tissue. An indication of more severe damage to the lung than pulmonary contusion, a hematoma also takes longer to clear. Unlike contusions, hematomas do not usually interfere with gas exchange in the lung, but they do increase the risk of infection and abscess formation.
Caplan syndrome presents with cough and shortness of breath in conjunction with features of rheumatoid arthritis, such as painful joints and morning stiffness.
Examination should reveal tender, swollen metacarpophalangeal joints and rheumatoid nodules; auscultation of the chest may reveal diffuse râles that do not disappear on coughing or taking a deep breath.
Caplan syndrome is a nodular condition of the lung occurring in dust-exposed persons with either a history of rheumatoid arthritis (RA) or who subsequently develop RA within the following 5–10 years. The nodules in the lung typically occur bilaterally and peripherally, on a background of simple coal workers' pneumoconiosis. There are usually multiple nodules, varying in size from 0.5 to 5.0 cm. The nodules typically appear rapidly, often in only a few weeks. Nodules may grow, remain unchanged in size, resolve, or disappear and then reappear. They can cavitate, calcify, or develop air-fluid levels. Grossly, they can resemble a giant silicotic nodule. Histologically, they usually have a necrotic center surrounded by a zone of plasma cells and lymphocytes, and often with a peripheral inflammatory zone made of macrophages and neutrophils.
Fire breather’s pneumonia usually presents with certain non-specific symptoms, and may vary significantly among individuals. The most common symptoms include:
- Cough
- Dyspnea (shortness of breath)
- Chest pain
- Fever
- Weakness
- Hemoptysis (coughing up blood)
Acute pneumonitis typically begins asymptomatic, with a worsening of symptoms over the course of hours or days. Following aspiration of fuel, there is often a period of latency from 8–24 hours before the symptoms occur. Patients may not recall a specific instance of aspiration. Severe cases may lead to acute respiratory distress syndrome (ARDS).
Caplan's syndrome (or Caplan disease or Rheumatoid pneumoconiosis) is a combination of rheumatoid arthritis (RA) and pneumoconiosis that manifests as intrapulmonary nodules, which appear homogenous and well-defined on chest X-ray.
Pulmonary neuroendocrine tumor are classified according to tumoral grade:
- Low grade pulmonary neuroendocrine tumor: Typical pulmonary carcinoid tumour (TC; low-grade);
- Intermediate-grade pulmonary neuroendocrine tumor: Atypical pulmonary carcinoid tumour (AC; intermediate-grade)
- High-grade pulmonary neuroendocrine tumor
- Small cell lung cancer (SCLC)
- Large cell neuroendocrine carcinoma (LCNEC of the lung)
Low-grade nodular neuroendocrine proliferations ≥ 0.5 cm are classified as carcinoid tumors and smaller ones are called pulmonary tumorlets.
When neuroendocrine cell hyperplasia and tumorlets are extensive, they represent the rare preinvasive lesion for carcinoids known as "diffuse idiopathic pulmonary neuroendocrine cell hyperplasia".
Both LCNEC and SCLC can demonstrate histologic heterogeneity with other major histologic types of lung carcinoma, such as pulmonary adenocarcinoma or pulmonary squamous cell carcinoma, but is not characteristic of TC or AC.
The disease has a long incubation period, and therefore signs usually occur in adult animals (over 2 years of age). Clinical signs resemble a non-specific progressive pneumonia, including poor body condition and, particularly after exercise, respiratory difficulty. Unless a concurrent lung infection is present, affected sheep continue to eat. The only sign specific to OPA is a watery nasal discharge, consisting of lung fluid produced by the affected lung tissue; lifting the hind legs of the animal above the level of its head will cause large volumes of this fluid to flow from the nostrils.
There are no reliable tests for the diagnosis of OPA in live animals which are suitable for use on farms, so diagnosis can only be confirmed at necropsy (post-mortem examination). On necropsy, lungs are interspersed with multifocal tumors. Some of these are small discrete nodules and others will involve the entire half of a lung lobule. JSRV acutely transforms the lung epithelia into cancerous cells, with type-2 pneumocytes and club cells being the likely target for JSRV transformation. The tumors have overactive secretory functions, which are a hallmark of OPA.
The retroviral antigen levels of JSRV are very high in OPA tumors and can be detected in the lung secretions of infected sheep. It is thought that infected animals secrete the virus before showing signs, so the virus is easily spread within flocks.
In medicine, nodules are solid, elevated areas of tissue or fluid inside or under the skin with a diameter greater than 0.5 centimeters. Nodules may form on tendons and muscles in response to injury. The vocal cords may also develop nodules. Nodules are normally benign and often painless, although they can affect the functioning of the organ.
Vocal fold nodules, thyroid nodules and rheumatoid nodules are examples. Furuncles and Kaposi's sarcomata are known to cause dermatological nodules.
The sexual transmitted disease (STD) gonorrhea is also known for its cause of nodules on the genitalia and mouth for those who are victim to the disease.
Smaller (less than 0.5 cm) elevated soft tissue lesions may be termed papules.
Thoracic endometriosis is characterised by onset of the following clinical situations within 24 hours prior to and 72 hours after onset of menses.
- Catamenial pneumothorax: this is the most common clinical manifestation, present in 80% of cases. Catamenial pneumothorax is defined as a recurrent pneumothorax that occurs within the first 72 hours after menstruation. It may not necessarily occur with every menstrual cycle and in most cases is one-sided and right side. There are particular cases of catamenial pneumothorax on the left side, and on very rare occasions there may be a bilateral catamenial pneumothorax. Symptoms are the same as for any other pneumothorax: chest pain, cough and breathlessness. Symptoms are usually mild but there may be severe presentations.
- Catamenial hemothorax: this is a rare manifestation of thoracic endometriosis, occurring in 14% of cases. Almost always, the right side is involved but has reported one case of a bilateral catamenial hemothorax. The most common presenting symptoms are nonspecific and include cough, chest pain and shortness of breath. In some cases, signs may mimic pulmonary embolism. The quantity of blood loss varies, but severe anemia is possible. In almost all cases, chest x-ray shows the presence of pleural effusion without specific characteristics. A CT scan may show additional features such as nodular lesions of the pleura, multiloculated effusions, or bulky pleural masses.
- Cyclic haemoptysis: haemoptysis during menstruation is extremely rare, with about 30 case reports in medical literature. Currently, there have been no reports of massive haemoptysis or death. Cyclic haemoptysis is a sign of pulmonary parenchymal endometriosis; ectopic endometrial tissue in the lung responds to cyclical hormonal variation, bleeding along with the normal endometrium located in the uterus.
- Pulmonary nodules: nodules are common radiological features in patients with thoracic endometriosis; most cases are associated with catamenial haemoptysis.
Apart from the previously mentioned clinical manifestations, the patient may suffer from dysmenorrhoea and irregular menses.
Pneumoconiosis is an occupational lung disease and a restrictive lung disease caused by the inhalation of dust, often in mines and from agriculture.
In 2013, it resulted in 260,000 deaths, up from 251,000 deaths in 1990. Of these deaths, 46,000 were due to silicosis, 24,000 due to asbestosis and 25,000 due to coal workers pneumoconiosis.
Positive indications on patient assessment:
- Shortness of breath
- Chest X-ray may show a characteristic patchy, subpleural, bibasilar interstitial infiltrates or small cystic radiolucencies called honeycombing.
Pneumoconiosis in combination with multiple pulmonary rheumatoid nodules in rheumatoid arthritis patients is known as Caplan's syndrome.