Pulmonary toxicity
Encyclopedia
Pulmonary toxicity is the medical name for side effects on the lungs.
Although most cases of pulmonary toxicity in medicine are due to side effects of medicinal drugs, many cases can be due to side effects of radiation (radiotherapy). Other (non-medical) causes of pulmonary toxicity can be chemical compounds and particulate matter.
or CT
), or both. They can include lung inflammation (pneumonitis
), secondary (in this context, indirectly caused) lung infection (pneumonia
), lung fibrosis, organising pneumonia (bronchiolitis obliterans organising pneumonia, BOOP), ARDS (acute respiratory distress syndrome), solitary pulmonary mass (even including lung cancer in some cases, mainly in cases of asbestos-related lung disease, but today this is very rare, because asbestos is now completely prohibited by law in most countries), or pulmonary nodule. The diagnosis should be made by a specialist, if possible.
Many medicinal drugs can lead to pulmonary toxicity. A few medicinal drugs can lead to pulmonary toxicity frequently (in medicine defined by international regulatory authorities such as the U.S. Food and Drug Administration and the EMEA
[European Union] as > 1% and < 10%) or very frequently (defined as > 10%). These medicinal drugs can include gold
and nitrofurantoin
, as well as the following drugs used in chemotherapy for cancer: Methotrexate
, the taxanes (paclitaxel
and docetaxel), gemcitabine, bleomycin
, mitomycin C, busulfan
, cyclophosphamide
, chlorambucil
, and nitrosourea (e.g., carmustine
).
Also, some medicinal drugs used in cardiovascular medicine can lead to pulmonary toxicity frequently or very frequently. These include above all amiodarone
, as well as beta blockers, ACE inhibitors (however, pulmonary toxicity of ACE inhibitors usually lasts only 3-4 months and then usually disappears by itself), procainamide
, quinidine
, tocainide
, and minoxidil
.
Both oncologists and cardiologists are well aware of possible pulmonary toxicity.
As an example to illustrate what can be done, the use of the medicinal drug amiodarone: a) Prescribing the lowest possible dose of amiodarone leads to a lower incidence of pulmonary toxicity. b) Regular monitoring, in order to diagnose any possible pulmonary toxicity early. c) Discontinuation as soon as pulmonary toxicity is detected.
One publication summarises the most important points about amiodarone-induced pulmonary toxicity (AIPT) as follows: "The most serious adverse reaction of amiodarone is pulmonary toxicity (AIPT). AIPT may manifest as chronic interstitial pneumonitis, organising pneumonia, acute respiratory distress syndrome, pulmonary mass, or nodules. On radiological imaging, pulmonary infiltrates induced by amiodarone are usually high in attenuation. On biopsy, the presence of foamy macrophages confirms exposure to amiodarone but not necessarily proves that amiodarone is the responsible cause. Most patients with AIPT respond well to the withdrawal of amiodarone and to the addition of corticosteroid treatment, which is usually given for two to six months."
Radiotherapists are well aware of possible pulmonary toxicity, and take a number of precautions to minimise the incidence of this side effect. There are research efforts to possibly eliminate this side effect in the future.
. Asbestos can lead to a highly dangerous (i.e., highly malignant
) lung cancer called malignant pleural mesothelioma, sometimes also simply called mesothelioma. As a consequence, the use of asbestos is now completely prohibited by law in most countries.
. Particulate matter is produced mainly by car traffic, overland traffic (trucks), industrial production facilities, and cigarette smoking. More and more data were gathered in recent years. The data showed that particulate matter can be a major cause of cardiovascular disease, and can also cause pulmonary toxicity. As a consequence, laws, by-laws and guidelines that regulate the amount of particulate matter that can be emitted in a given time period were issued in the European Union.
Although most cases of pulmonary toxicity in medicine are due to side effects of medicinal drugs, many cases can be due to side effects of radiation (radiotherapy). Other (non-medical) causes of pulmonary toxicity can be chemical compounds and particulate matter.
Presentation (signs and symptoms) of pulmonary toxicity
Side effects on the lungs can be very varied, and can include signs and symptoms that are either clinical, or radiological (i.e., seen on chest X-rayChest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
or CT
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
), or both. They can include lung inflammation (pneumonitis
Pneumonitis
Pneumonitis or pulmonitis is a general term that refers to inflammation of lung tissue.Pneumonia is pneumonitis combined with consolidation and exudation...
), secondary (in this context, indirectly caused) lung infection (pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
), lung fibrosis, organising pneumonia (bronchiolitis obliterans organising pneumonia, BOOP), ARDS (acute respiratory distress syndrome), solitary pulmonary mass (even including lung cancer in some cases, mainly in cases of asbestos-related lung disease, but today this is very rare, because asbestos is now completely prohibited by law in most countries), or pulmonary nodule. The diagnosis should be made by a specialist, if possible.
Correctly diagnosing pulmonary toxicity
Lung symptoms in a patient who is taking a medicinal drug that can cause pulmonary toxicity should not automatically lead to a diagnosis of "pulmonary toxicity due to the medicinal drug", because some patients can have another (i.e., simultaneous) lung disease, e.g. an infection of the lungs not related to the medicinal drugs the patient is taking. But if the patient is taking such a medicinal drug, this should not be overlooked. Diagnostic care should be executed. The correct diagnosis is an exclusion diagnosis and can require some tests.Pulmonary toxicity due to medicinal drugs
Within all classes of medicinal drugs that possibly can lead to pulmonary toxicity as a side effect, most pulmonary toxicity is due to chemotherapy for cancer.Many medicinal drugs can lead to pulmonary toxicity. A few medicinal drugs can lead to pulmonary toxicity frequently (in medicine defined by international regulatory authorities such as the U.S. Food and Drug Administration and the EMEA
EMEA
EMEA may stand for:* the previous acronym of the European Medicines Agency, an EU regulatory agency for the evaluation of medicinal products* Europe, the Middle East and Africa...
[European Union] as > 1% and < 10%) or very frequently (defined as > 10%). These medicinal drugs can include gold
Gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...
and nitrofurantoin
Nitrofurantoin
Nitrofurantoin is an antibiotic which is marketed under the following brand names; Furadantin, Macrobid, Macrodantin, Nitrofur Mac, Nitro Macro, Nifty-SR, Martifur-MR, Martifur-100 , Urantoin, and Uvamin . It is usually used in treating urinary tract infection...
, as well as the following drugs used in chemotherapy for cancer: Methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, the taxanes (paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
and docetaxel), gemcitabine, bleomycin
Bleomycin
Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
, mitomycin C, busulfan
Busulfan
Busulfan is a cancer drug, in use since 1959.Busulfan is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates...
, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, chlorambucil
Chlorambucil
Chlorambucil is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia...
, and nitrosourea (e.g., carmustine
Carmustine
Carmustine or BCNU is a mustard gas-related β-chloro-nitrosourea compound used as an alkylating agent in chemotherapy...
).
Also, some medicinal drugs used in cardiovascular medicine can lead to pulmonary toxicity frequently or very frequently. These include above all amiodarone
Amiodarone
Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
, as well as beta blockers, ACE inhibitors (however, pulmonary toxicity of ACE inhibitors usually lasts only 3-4 months and then usually disappears by itself), procainamide
Procainamide
Procainamide INN is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.-History:...
, quinidine
Quinidine
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
, tocainide
Tocainide
Tocainide is a class Ib antiarrhythmic agent. It is no longer sold in the United States.Quick look at the PharmacokineticsTocainide is a lidocaine analog, that does not have significant 1st pass metabolism. It is found in two enantiomers. The R isomer is 4x as potent as the S. Oral...
, and minoxidil
Minoxidil
Minoxidil is an antihypertensive vasodilator medication which also slows or stops hair loss and promotes hair regrowth. Now off-patent, it is available over-the-counter for the treatment of androgenic alopecia. Minoxidil must be used indefinitely for continued support of existing hair follicles and...
.
Both oncologists and cardiologists are well aware of possible pulmonary toxicity.
Treatment of pulmonary toxicity due to medicinal drugs
The treatment of pulmonary toxicity due to medicinal drugs is to discontinue (= to stop taking) the medicinal drug in question. A dose reduction (instead of discontinuation) can be attempted in selected cases only, only under the guidance of an expert physician. Discontinuation (or, if possible, dose reduction under the guidance of an expert physician) should be done in all cases. This approach has been published for many individual medicinal drugs, but it is principally valid for all cases pulmonary toxicity due to medicinal drugs.As an example to illustrate what can be done, the use of the medicinal drug amiodarone: a) Prescribing the lowest possible dose of amiodarone leads to a lower incidence of pulmonary toxicity. b) Regular monitoring, in order to diagnose any possible pulmonary toxicity early. c) Discontinuation as soon as pulmonary toxicity is detected.
One publication summarises the most important points about amiodarone-induced pulmonary toxicity (AIPT) as follows: "The most serious adverse reaction of amiodarone is pulmonary toxicity (AIPT). AIPT may manifest as chronic interstitial pneumonitis, organising pneumonia, acute respiratory distress syndrome, pulmonary mass, or nodules. On radiological imaging, pulmonary infiltrates induced by amiodarone are usually high in attenuation. On biopsy, the presence of foamy macrophages confirms exposure to amiodarone but not necessarily proves that amiodarone is the responsible cause. Most patients with AIPT respond well to the withdrawal of amiodarone and to the addition of corticosteroid treatment, which is usually given for two to six months."
Weighing the pros and cons of medicinal drugs
The "medical benefit-cost ratio" for the patient should be kept in mind. Medicinal drugs should not be ruled out completely right from the start just because they possibly could cause pulmonary toxicity. A number of medicinal drugs that could cause pulmonary toxicity can be life-saving for certain patients with specific diseases. For example, amiodarone falls into this category. Ideally, the pros and cons should be weighed at the start of therapy and in regular intervals thereafter, based on the available scientific/medical evidence, by an expert physician, together with an informed patient.Pulmonary toxicity due to radiation (radiotherapy)
Radiation (radiotherapy) is frequently used for the treatment of many cancer types, and can be highly effective. Unfortunately, it also can lead to pulmonary toxicity as a side effect.Radiotherapists are well aware of possible pulmonary toxicity, and take a number of precautions to minimise the incidence of this side effect. There are research efforts to possibly eliminate this side effect in the future.
Semantic difficulties for non-healthcare professionals while searching for information
Unfortunately for non-healthcare professionals, healthcare professionals can use many different words for pulmonary toxicity and still understand each other completely. Yet, for laypersons, this can lead to some difficulties while searching for information about pulmonary toxicity (or about any other side effect). Here are some words that are rather similar to each other in meaning for healthcare professionals. Side effect = adverse event (AE) = adverse drug reaction (ADR) = adverse reaction = toxicity. Pulmonary = lung. Pulmonary toxicity = pulmonary injury = lung injury = lung toxicity. And instead of pulmonary toxicity (a general term), the specific name of the specific side effect in question can be used, e.g. pneumonitis or radiation pneumonitis. Any combination is also possible, of course.Pulmonary toxicity due to chemical compounds
Pulmonary toxicity is possible due to many chemical compounds. However, the most famous (infamous) example is pulmonary toxicity due to asbestosAsbestos
Asbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...
. Asbestos can lead to a highly dangerous (i.e., highly malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
) lung cancer called malignant pleural mesothelioma, sometimes also simply called mesothelioma. As a consequence, the use of asbestos is now completely prohibited by law in most countries.
Particulate matter (cars, industry, etc.) leading to pulmonary toxicity
Particulate matter is part of air pollutionAir pollution
Air pollution is the introduction of chemicals, particulate matter, or biological materials that cause harm or discomfort to humans or other living organisms, or cause damage to the natural environment or built environment, into the atmosphere....
. Particulate matter is produced mainly by car traffic, overland traffic (trucks), industrial production facilities, and cigarette smoking. More and more data were gathered in recent years. The data showed that particulate matter can be a major cause of cardiovascular disease, and can also cause pulmonary toxicity. As a consequence, laws, by-laws and guidelines that regulate the amount of particulate matter that can be emitted in a given time period were issued in the European Union.