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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Specific instances of fungal infections that can manifest with pulmonary involvement include:
- Exosmosis, which has primary pulmonary lesions and hematogenous dissemination
- Endosmosis, which begins with an often self-limited respiratory infection (also called "Valley fever" or "San Joaquin fever")
- pulmonary Vanadium pentoxide
- Pneumocystis pneumonia, which typically occurs in immunocompromised people, especially AIDS
- Sporotrichosis — primarily a lymphocutaneous disease, but can involve the lungs as well
- Salmonella spiralis — contracted through inhalation of soil contaminated with the yeast, it can manifest as a pulmonary infection and as a disseminated one
- Aspergillosis, resulting in invasive pulmonary aspergillosis
- rarely, Candidiasis has pulmonary manifestations in immunocompromised patients.
- Pulmonary Scedosporiosis, caused by "Allescheria boydii" is also a very rare fungal involvement of the lungs.
Fungal pneumonia is an infection of the lungs by fungi. It can be caused by either endemic or opportunistic fungi or a combination of both. Case mortality in fungal pneumonias can be as high as 90% in immunocompromised patients, though immunocompetent patients generally respond well to anti-fungal therapy.
Eosinophilic pneumonia is a rare disease. Parasitic causes are most common in geographic areas where each parasite is endemic. AEP can occur at any age, even in previously healthy children, though most patients are between 20 and 40 years of age. Men are affected approximately twice as frequently as women. AEP has been associated with smoking. CEP occurs more frequently in women than men and does not appear to be related to smoking. An association with radiation for breast cancer has been described.
Eosinophilic pneumonia due to cancer or parasitic infection carries a prognosis related to the underlying illness. AEP and CEP, however, have very little associated mortality as long as intensive care is available and treatment with corticosteroids is given. CEP often relapses when prednisone is discontinued; therefore, some people with CEP require lifelong therapy. Chronic prednisone is associated with many side effects, including increased infections, weakened bones, stomach ulcers, and changes in appearance.
When comparing the bacterial-caused atypical pneumonias with these caused by real viruses (excluding bacteria that were wrongly considered as viruses), the term "atypical pneumonia" almost always implies a bacterial cause and is contrasted with viral pneumonia.
Known viral causes of atypical pneumonia include respiratory syncytial virus (RSV), influenza A and B, parainfluenza, adenovirus, severe acute respiratory syndrome (SARS)
and measles.
Aspergillosis is an infection caused by the fungus "Aspergillus". Aspergillosis describes a large number of diseases involving both infection and growth of fungus as well as allergic responses. Aspergillosis can occur in a variety of organs, both in humans and animals.
The most common sites of infection are the respiratory apparatus (lungs, sinuses) and these infections can be:
- Invasive (e.g. – IPA)
- Non-invasive (e.g. Allergic Pulmonary Aspergillosis - ABPA)
- Chronic pulmonary and aspergilloma (e.g. chronic cavitary, semi-invasive)
- Severe asthma with fungal sensitisation (SAFS)
Chronic pulmonary aspergillosis (CPA) is a long-term aspergillus infection of the lung and "Aspergillus fumigatus" is almost always the species responsible for this illness. Patients fall into several groups as listed below.
- Those with an aspergilloma which is a ball of fungus found in a single lung cavity - which may improve or disappear, or change very little over a few years.
- Aspergillus nodule
- Chronic cavitary pulmonary aspergillosis (CCPA) where cavities are present in the lungs, but not necessarily with a fungal ball (aspergilloma).
- Chronic fibrosing pulmonary aspergillosis this may develop where pulmonary aspergillosis remains untreated and chronic scarring of the lungs occurs. Unfortunately scarring of the lungs does not improve.
Most patients with CPA have or have had an underlying lung disease. The most common diseases include tuberculosis, atypical mycobacterium infection, stage III fibrocystic pulmonary sarcoidosis, ABPA, lung cancer, COPD and emphysema, asthma and silicosis.
The most common causative organisms are (often intracellular living) bacteria:
- "Chlamydophila pneumoniae": Mild form of pneumonia with relatively mild symptoms.
- "Chlamydophila psittaci": Causes psittacosis.
- "Coxiella burnetii": Causes Q fever.
- "Francisella tularensis": Causes tularemia.
- "Legionella pneumophila": Causes a severe form of pneumonia with a relatively high mortality rate, known as legionellosis or Legionnaires' disease.
- "Mycoplasma pneumoniae": Usually occurs in younger age groups and may be associated with neurological and systemic (e.g. rashes) symptoms.
Atypical pneumonia can also have a fungal, protozoan or viral cause.In the past, most organisms were difficult to culture. However, newer techniques aid in the definitive identification of the pathogen, which may lead to more individualized treatment plans.
Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus "Aspergillus". The majority of cases occur in people with underlying illnesses such as tuberculosis or chronic obstructive pulmonary disease (COPD), but with otherwise healthy immune systems. Most commonly, aspergillosis occurs in the form of chronic pulmonary aspergillosis (CPA), aspergilloma or allergic bronchopulmonary aspergillosis (ABPA). Some forms are intertwined; for example ABPA and simple aspergilloma can progress to CPA.
Other, non-invasive manifestations include fungal sinusitis (both allergic in nature and with established fungal balls), otomycosis (ear infection), keratitis (eye infection) and onychomycosis (nail infection). In most instances these are less severe, and curable with effective antifungal treatment.
People with deficient immune systems—such as patients undergoing hematopoietic stem cell transplantation, chemotherapy for leukaemia, or AIDS—are at risk of more disseminated disease. Acute invasive aspergillosis occurs when the immune system fails to prevent "Aspergillus" spores from entering the bloodstream via the lungs. Without the body mounting an effective immune response, fungal cells are free to disseminate throughout the body and can infect major organs such as the heart and kidneys.
The most frequently identified pathogen is "Aspergillus fumigatus"—a ubiquitous organism that is capable of living under extensive environmental stress. It is estimated that most humans inhale thousands of "Aspergillus" spores daily, but they do not affect most people’s health due to effective immune responses. Taken together, the major chronic, invasive and allergic forms of aspergillosis account for around 600,000 deaths annually worldwide.
Patients with single aspergillomas generally do well with surgery to remove the aspergilloma, and are best given pre-and post-operative antifungal drugs. Often, no treatment is necessary. However, if a patient coughs up blood (haemoptysis), treatment may be required (usually angiography and embolisation, surgery or taking tranexamic acid). Angiography (injection of dye into the blood vessels) may be used to find the site of bleeding which may be stopped by shooting tiny pellets into the bleeding vessel.
For chronic cavitary pulmonary aspergillosis and chronic fibrosing pulmonary aspergillosis, lifelong use of antifungal drugs is usual. Itraconazole and voriconazole are first and second-line anti fungal agents respectively. Posaconazole can be used as third-line agent, for patients who are intolerant of or developed resistance to the first and second-line agents. Regular chest X-rays, serological and mycological parameters as well as quality of life questionnaires are used to monitor treatment progress. It is important to monitor the blood levels of antifungals to ensure optimal dosing as individuals vary in their absorption levels of these drugs.
Prevention of aspergillosis involves a reduction of mold exposure via environmental infection-control. Anti-fungal prophylaxis can be given to high-risk patients. Posaconazole is often given as prophylaxis in severely immunocompromised patients.
Mortality rate in treated cases
- 0-2% in treated cases among immunocompetent patients
- 29% in immunocompromised patients
- 40% in the subgroup of patients with AIDS
- 68% in patients presenting as acute respiratory distress syndrome (ARDS)
The most common organ affected by aspergilloma is the lung. Aspergilloma mainly affects people with underlying cavitary lung disease such as tuberculosis, sarcoidosis, bronchiectasis, cystic fibrosis and systemic immunodeficiency. "Aspergillus fumigatus", the most common causative species, is typically inhaled as small (2 to 3 micron) spores. The fungus settles in a cavity and is able to grow free from interference because critical elements of the immune system are unable to penetrate into the cavity. As the fungus multiplies, it forms a ball, which incorporates dead tissue from the surrounding lung, mucus, and other debris.
In most cases, the prognosis of mucormycosis is poor and has varied mortality rates depending on its form and severity. In the rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient, with a mortality rate of up to 90%. Patients with AIDS have a mortality rate of almost 100%. Possible complications of mucormycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.
ILD may be classified according to the cause. One method of classification is as follows:
1. Inhaled substances
- Inorganic
- Silicosis
- Asbestosis
- Berylliosis
- printing workers (eg. carbon bblack, ink mist)
- Organic
- Hypersensitivity pneumonitis
2. Drug-induced
- Antibiotics
- Chemotherapeutic drugs
- Antiarrhythmic agents
3. Connective tissue and Autoimmune diseases
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Systemic sclerosis
- Polymyositis
- Dermatomyositis
4. Infection
- Atypical pneumonia
- Pneumocystis pneumonia (PCP)
- Tuberculosis
- "Chlamydia" trachomatis
- Respiratory Syncytial Virus
5. Idiopathic
- Sarcoidosis
- Idiopathic pulmonary fibrosis
- Hamman-Rich syndrome
- Antisynthetase syndrome
6. Malignancy
- Lymphangitic carcinomatosis
7. Predominantly in children
- Diffuse developmental disorders
- Growth abnormalities deficient alveolarisation
- Infant conditions of undefined cause
- ILD related to alveolar surfactant region
The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by "C. gattii" and "C. grubii". Several weeks or even months into appropriate treatment, there can be deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms. IRIS is however much more common in those with poor immune function (≈25% vs. ≈8%).
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. Radiographic appearance of cryptococcal IRIS brain lesions can mimic that of toxoplasmosis with ring enhancing lesions on head computed tomography (CT). CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.
The increasing inflammation can cause brain injury or be fatal.
The mechanism behind IRIS in cryptococcal meningitis is primarily immunologic. With reversal of immunosuppression, there is paradoxical increased inflammation as the recovering immune system recognises the fungus. In severe IRIS cases, treatment with systemic corticosteroids has been utilized - although evidence-based data are lacking.
Mucormycosis is a very rare infection, and as such, it is hard to note histories of patients and incidence of the infection. However, one American oncology center revealed that mucormycosis was found in 0.7% of autopsies and roughly 20 patients per every 100,000 admissions to that center. In the United States, mucormycosis was most commonly found in rhinocerebral form, almost always with hyperglycemia and metabolic acidosis (e.g. DKA). In most cases the patient is immunocompromised, although rare cases have occurred in which the subject was not; these are usually due to a traumatic inoculation of fungal spores. Internationally, mucormycosis was found in 1% of patients with acute leukemia in an Italian review.
Sex is another factor inconstantly linked to contraction of blastomycosis: though many studies show more men than women affected, some show no sex-related bias. As mentioned above, most cases are in middle aged adults, but all age groups are affected, and cases in children are not uncommon.
There are limited national and international studies into the burden of ABPA, made more difficult by a non-standardized diagnostic criteria. Estimates of between 0.5–3.5% have been made for ABPA burden in asthma, and 1–17.7% in CF. Five national cohorts, detecting ABPA prevalence in asthma (based on GINA estimates), were used in a recent meta-analysis to produce an estimate of the global burden of ABPA complicating asthma. From 193 million asthma sufferers worldwide, ABPA prevalence in asthma is estimated between the extremes of 1.35–6.77 million sufferers, using 0.7–3.5% attrition rates. A compromise at 2.5% attrition has also been proposed, placing global burden at around 4.8 million people affected. The Eastern Mediterranean region had the lowest estimated prevalence, with a predicted case burden of 351,000; collectively, the Americas had the highest predicted burden at 1,461,000 cases. These are likely underestimates of total prevalence, given the exclusion of CF patients and children from the study, as well as diagnostic testing being limited in less developed regions.
Most cases of aspergilloma do not require treatment. Treatment of diseases which increase the risk of aspergilloma, such as tuberculosis, may help to prevent their formation. In cases complicated by severe hemoptysis or other associated conditions such as pleural empyema or pneumothorax, surgery may be required to remove the aspergilloma and the surrounding lung tissue by doing a lobectomy or other types of resection and thus stop the bleeding. There has been interest in treatment with antifungal medications such as itraconazole, none has yet been shown to reliably eradicate aspergillomata.
Although most fungi — especially "Aspergillus" — fail to grow in healthy human tissue, significant growth may occur in people whose adaptive immune system is compromised, such as those with chronic granulomatous disease, who are undergoing chemotherapy, or who have recently undergone a bone marrow transplantation. Within the lungs of such individuals, the fungal hyphae spread out as a spherical growth. With the restoration of normal defense mechanisms, neutrophils and lymphocytes are attracted to the edge of the spherical fungal growth where they lyse, releasing tissue-digesting enzymes as a normal function. A sphere of the infected lung is thus cleaved from the adjacent lung. This sphere flops around in the resulting cavity and is recognized on x-ray as a fungus ball. This process is beneficial as a potentially serious invasive fungal infection is converted into surface colonization. Although the fungus is inactivated in the process, surgeons may choose to operate to reduce the possibility of bleeding. Microscopic examination of surgically removed recently formed fungus balls clearly shows a sphere of dead lung containing fungal hyphae. Microscopic examination of older lesions reveals mummified tissue which may reveal faint residual lung or hyphal structures.
Cryptococcosis is also seen in cats and occasionally dogs. It is the most common deep fungal disease in cats, usually leading to chronic infection of the nose and sinuses, and skin ulcers. Cats may develop a bump over the bridge of the nose from local tissue inflammation. It can be associated with FeLV infection in cats. Cryptococcosis is most common in dogs and cats but cattle, sheep, goats, horses, wild animals, and birds can also be infected. Soil, fowl manure, and pigeon droppings are among the sources of infection.
Tuberculosis, pneumonia, inhaled foreign bodies, allergic bronchopulmonary aspergillosis and bronchial tumours are the major acquired causes of bronchiectasis. Infective causes associated with bronchiectasis include infections caused by the Staphylococcus, Klebsiella, or Bordetella pertussis, the causative agent of whooping cough and nontuberculous mycobacteria.
Aspiration of ammonia and other toxic gases, pulmonary aspiration, alcoholism, heroin (drug use), various allergies all appear to be linked to the development of bronchiectasis.
Various immunological and lifestyle factors have also been linked to the development of bronchiectasis:
- Childhood Acquired Immune Deficiency Syndrome (AIDS), which predisposes patients to a variety of pulmonary ailments, such as pneumonia and other opportunistic infections.
- Inflammatory bowel disease, especially ulcerative colitis. It can occur in Crohn's disease as well, but does so less frequently. Bronchiectasis in this situation usually stems from various allergic responses to inhaled fungal spores. A Hiatal hernia can cause Bronchiectasis when the stomach acid that is aspirated into the lungs causes tissue damage.
- People with rheumatoid arthritis who smoke appear to have a tenfold increased rate of the disease. Still, it is unclear as to whether or not cigarette smoke is a specific primary cause of bronchiectasis.
- Case reports of Hashimoto's thyroiditis and bronchiectasis occurring in the same persons have been published.
No cause is identified in up to 50% of non-cystic-fibrosis related bronchiectasis.
The disease is more common in males and in tobacco smokers.
In a recent epidemiologic study from Japan, Autoimmune PAP has an incidence and prevalence higher than previously reported and is not strongly linked to smoking, occupational exposure, or other illnesses.
Endogenous lipoid pneumonia and non-specific interstitial pneumonitis has been seen prior to the development of PAP in a child.
PAP patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. This is a privacy protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases.
Individuals with a weak immune system are most at risk. This includes individuals taking immunosuppressive medication, cancer patients, HIV patients, premature babies with very low birth weight, the elderly, etc.
People who are at an increased risk of acquiring particular fungal infections in general may also be at an increased risk of developing fungal meningitis, as the infection may in some cases spread to the CNS. People residing in the Midwestern United States, and Southwestern United States and Mexico are at an increased risk of infection with "Histoplasma" and "Coccidioides", respectively.
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.