Diagnosis of sarcoidosis is a matter of exclusion, as there is no specific test for the condition. To exclude sarcoidosis in a case presenting with pulmonary symptoms might involve a chest radiograph, CT scan of chest, PET scan, CT-guided biopsy, mediastinoscopy, open lung biopsy, bronchoscopy with biopsy, endobronchial ultrasound, and endoscopic ultrasound with fine-needle aspiration of mediastinal lymph nodes (EBUS FNA). Tissue from biopsy of lymph nodes is subjected to both flow cytometry to rule out cancer and special stains (acid fast bacilli stain and Gömöri methenamine silver stain) to rule out microorganisms and fungi.

Serum markers of sarcoidosis, include: serum amyloid A, soluble interleukin-2 receptor, lysozyme, angiotensin converting enzyme, and the glycoprotein KL-6. Angiotensin-converting enzyme blood levels are used in the monitoring of sarcoidosis. A bronchoalveolar lavage can show an elevated (of at least 3.5) CD4/CD8 T cell ratio, which is indicative (but not proof) of pulmonary sarcoidosis. In at least one study the induced sputum ratio of CD4/CD8 and level of TNF was correlated to those in the lavage fluid. A sarcoidosis-like lung disease called granulomatous–lymphocytic interstitial lung disease can be seen in patients with common variable immunodeficiency (CVID) and therefore serum antibody levels should be measured to exclude CVID.

Differential diagnosis includes metastatic disease, lymphoma, septic emboli, rheumatoid nodules, granulomatosis with polyangiitis, varicella infection, tuberculosis, and atypical infections, such as "Mycobacterium avium" complex, cytomegalovirus, and cryptococcus. Sarcoidosis is confused most commonly with neoplastic diseases, such as lymphoma, or with disorders characterized also by a mononuclear cell granulomatous inflammatory process, such as the mycobacterial and fungal disorders.

Chest radiograph changes are divided into four stages:

1. bihilar lymphadenopathy

2. bihilar lymphadenopathy and reticulonodular infiltrates

3. bilateral pulmonary infiltrates

4. fibrocystic sarcoidosis typically with upward hilar retraction, cystic and bullous changes

Although people with stage 1 radiographs tend to have the acute or subacute, reversible form of the disease, those with stages 2 and 3 often have the chronic, progressive disease; these patterns do not represent consecutive "stages" of sarcoidosis. Thus, except for epidemiologic purposes, this categorization is mostly of historic interest.

In sarcoidosis presenting in the Caucasian population, hilar adenopathy and erythema nodosum are the most common initial symptoms. In this population, a biopsy of the gastrocnemius muscle is a useful tool in correctly diagnosing the person. The presence of a noncaseating epithelioid granuloma in a gastrocnemius specimen is definitive evidence of sarcoidosis, as other tuberculoid and fungal diseases extremely rarely present histologically in this muscle.

Sarcoidosis may be divided into the following types:

- Annular sarcoidosis

- Erythrodermic sarcoidosis

- Ichthyosiform sarcoidosis

- Hypopigmented sarcoidosis

- Löfgren syndrome

- Lupus pernio

- Morpheaform sarcoidosis

- Mucosal sarcoidosis

- Neurosarcoidosis

- Papular sarcoid

- Scar sarcoid

- Subcutaneous sarcoidosis

- Systemic sarcoidosis

- Ulcerative sarcoidosis

The diagnosis of retroperitoneal fibrosis cannot be made on the basis of results of laboratory studies. CT is the best diagnostic modality: a confluent mass surrounding the aorta can be seen on a CT scan. Although biopsy is not usually recommended, it is appropriate when malignancy or infection is suspected. Biopsy should also be done if the location of fibrosis is atypical or if there is an inadequate response to initial treatment.

The diagnosis of neurosarcoidosis often is difficult. Definitive diagnosis can only be made by biopsy (surgically removing a tissue sample). Because of the risks associated with brain biopsies, they are avoided as much as possible. Other investigations that may be performed in any of the symptoms mentioned above are computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, lumbar puncture, electroencephalography (EEG) and evoked potential (EP) studies. If the diagnosis of sarcoidosis is suspected, typical X-ray or CT appearances of the chest may make the diagnosis more likely; elevations in angiotensin-converting enzyme and calcium in the blood, too, make sarcoidosis more likely. In the past, the Kveim test was used to diagnose sarcoidosis. This now obsolete test had a high (85%) sensitivity, but required spleen tissue of a known sarcoidosis patient, an extract of which was injected into the skin of a suspected case.

Only biopsy of suspicious lesions in the brain or elsewhere is considered useful for a definitive diagnosis of neurosarcoid. This would demonstrate granulomas (collections of inflammatory cells) rich in epithelioid cells and surrounded by other immune system cells (e.g. plasma cells, mast cells). Biopsy may be performed to distinguish mass lesions from tumours (e.g. gliomas).

MRI with gadolinium enhancement is the most useful neuroimaging test. This may show enhancement of the pia mater or white matter lesions that may resemble the lesions seen in multiple sclerosis.

Lumbar puncture may demonstrate raised protein level, pleiocytosis (i.e. increased presence of both lymphocytes and neutrophil granulocytes) and oligoclonal bands. Various other tests (e.g. ACE level in CSF) have little added value.

Some recent papers propose to classify neurosarcoidosis by likelihood:

- "Definite" neurosarcoidosis can only be diagnosed by plausible symptoms, a positive biopsy and no other possible causes for the symptoms

- "Probable" neurosarcoidosis can be diagnosed if the symptoms are suggestive, there is evidence of central nervous system inflammation (e.g. CSF and MRI), and other diagnoses have been excluded. A diagnosis of systemic sarcoidosis is not essential.

- "Possible" neurosarcoidosis may be diagnosed if there are symptoms not due to other conditions but other criteria are not fulfilled.

Diagnosis is typically made via echocardiography. Patients will demonstrate normal systolic function, diastolic dysfunction, and a restrictive filling pattern. 2-dimensional and Doppler studies are necessary to distinguish RCM from constrictive pericarditis. Cardiac MRI and transvenous endomyocardial biopsy may also be necessary in some cases. Reduced QRS voltage on EKG may be an indicator of amyloidosis-induced restrictive cardiomyopathy.

Cardiac arrest is synonymous with clinical death.

A cardiac arrest is usually diagnosed clinically by the absence of a pulse. In many cases lack of carotid pulse is the gold standard for diagnosing cardiac arrest, as lack of a pulse (particularly in the peripheral pulses) may result from other conditions (e.g. shock), or simply an error on the part of the rescuer. Nonetheless, studies have shown that rescuers often make a mistake when checking the carotid pulse in an emergency, whether they are healthcare professionals or lay persons.

Owing to the inaccuracy in this method of diagnosis, some bodies such as the European Resuscitation Council (ERC) have de-emphasised its importance. The Resuscitation Council (UK), in line with the ERC's recommendations and those of the American Heart Association,

have suggested that the technique should be used only by healthcare professionals with specific training and expertise, and even then that it should be viewed in conjunction with other indicators such as agonal respiration.

Various other methods for detecting circulation have been proposed. Guidelines following the 2000 International Liaison Committee on Resuscitation (ILCOR) recommendations were for rescuers to look for "signs of circulation", but not specifically the pulse. These signs included coughing, gasping, colour, twitching and movement. However, in face of evidence that these guidelines were ineffective, the current recommendation of ILCOR is that cardiac arrest should be diagnosed in all casualties who are unconscious and not breathing normally. Another method is to use molecular autopsy or postmortem molecular testing which uses a set of molecular techniques to find the ion channels that are cardiac defective.

Clinicians classify cardiac arrest into "shockable" versus "non–shockable", as determined by the ECG rhythm. This refers to whether a particular class of cardiac dysrhythmia is treatable using defibrillation. The two "shockable" rhythms are ventricular fibrillation and pulseless ventricular tachycardia while the two "non–shockable" rhythms are asystole and pulseless electrical activity.

In the absence of severe urinary tract obstruction (which generally requires surgery with omental wrapping), treatment is generally with glucocorticoids initially, followed by DMARDs either as steroid-sparing agents or if refractory on steroids. The SERM tamoxifen has shown to improve the condition in various small trials, although the exact mechanism of its action remains unclear.

Associations include:

- Riedel's thyroiditis

- previous radiotherapy

- sarcoidosis

- inflammatory abdominal aortic aneurysm

- drugs

ARVD is an autosomal dominant trait with reduced penetrance. Approximately 40–50% of ARVD patients have a mutation identified in one of several genes encoding components of the desmosome, which can help confirm a diagnosis of ARVD. Since ARVD is an autosomal dominant trait, children of an ARVD patient have a 50% chance of inheriting the disease causing mutation. Whenever a mutation is identified by genetic testing, family-specific genetic testing can be used to differentiate between relatives who are at-risk for the disease and those who are not. ARVD genetic testing is clinically available.

The cause of development for cardiac fibroma is still unknown or unexplained. Some of these cases are observed to be linked to Gorlin syndrome; a complex genetic disorder causing the formation of tumors in various parts of the body. Research is currently being undertaken to identify relevant casual factors. Currently, there are no known methods for preventing cardiac fibroma.

The following tests and exams are taken to diagnose Cardiac fibroma:

1. Family medical history and thorough physical examination that includes examination of the heart. Close attention to abnormal heart sounds is important.

2. Echocardiography: Most valuable diagnosis because this can evaluate the morphology, location and range of the tumor. Also, it can access the degree of blood flow obstruction caused by tumor.

3. Magnetic Resonance Imaging (MRI) and computed tomography CT scan of the heart

4. Electrocardiogram (EKG): this is used to measure electrical activity of the heart and to detect arrhythmias.

5. Electrophysiological studies of an individuals heart to determine where arrhythmia is generated in the heart.

6. Doppler ultrasound to measure the speed and direction of blood flow from sound waves.

7. Tissue biopsy: a pathologist may examine the biopsy under a microscope to suggest a definitive diagnosis. This is considered a gold standard in arriving to a conclusive diagnosis. Biopsy specimens are studied by using Hematoxylin and Eosin staining.

Generalized enlargement of the heart is seen upon normal chest X-ray. Pleural effusion may also be noticed, which is due to pulmonary venous hypertension.

The electrocardiogram often shows sinus tachycardia or atrial fibrillation, ventricular arrhythmias, left atrial enlargement, and sometimes intraventricular conduction defects and low voltage. When left bundle-branch block (LBBB) is accompanied by right axis deviation (RAD), the rare combination is considered to be highly suggestive of dilated or congestive cardiomyopathy. Echocardiogram shows left ventricular dilatation with normal or thinned walls and reduced ejection fraction. Cardiac catheterization and coronary angiography are often performed to exclude ischemic heart disease.

Genetic testing can be important, since one study has shown that gene mutations in the TTN gene (which codes for a protein called titin) are responsible for "approximately 25% of familial cases of idiopathic dilated cardiomyopathy and 18% of sporadic cases." The results of the genetic testing can help the doctors and patients understand the underlying cause of the dilated cardiomyopathy. Genetic test results can also help guide decisions on whether a patient's relatives should undergo genetic testing (to see if they have the same genetic mutation) and cardiac testing to screen for early findings of dilated cardiomyopathy.

Cardiac magnetic resonance imaging (cardiac MRI) may also provide helpful diagnostic information in patients with dilated cardiomyopathy.

In general, the minimal evaluation of atrial fibrillation should be performed in all individuals with AF. The goal of this evaluation is to determine the general treatment regimen for the individual. If results of the general evaluation warrant it, further studies may then be performed.

Ambulatory monitoring of the electrocardiogram (ECG) may be necessary because arrhythmias are transient. The ECG may show any of the following:

- Inappropriate sinus bradycardia

- Sinus arrest

- Sinoatrial block

- Tachy-Brady Syndrome

- Atrial fibrillation with slow ventricular response

- A prolonged asystolic period after a period of tachycardias

- Atrial flutter

- Ectopic atrial tachycardia

- Sinus node reentrant tachycardia

- Wolff-Parkinson-White syndrome

Electrophysiologic tests are no longer used for diagnostic purposes because of their low specificity and sensitivity. Cardioinhibitory and vasodepressor forms of sick sinus syndrome may be revealed by tilt table testing.

Limited studies have suggested that screening for atrial fibrillation in those 65 years and older increases the number of cases of atrial fibrillation detected.

Treatment of restrictive cardiomyopathy should focus on management of causative conditions (for example, using corticosteroids if the cause is sarcoidosis), and slowing the progression of cardiomyopathy. Salt-restriction, diuretics, angiotensin-converting enzyme inhibitors, and anticoagulation may be indicated for managing restrictive cardiomyopathy.

Calcium channel blockers are generally contraindicated due to their negative inotropic effect, particularly in cardiomyopathy caused by amyloidosis. Digoxin, calcium channel blocking drugs and beta-adrenergic blocking agents provide little benefit, except in the subgroup of restrictive cardiomyopathy with atrial fibrillation. Vasodilators are also typically ineffective because systolic function is usually preserved in cases of RCM.

Heart failure resulting from restrictive cardiomyopathy will usually eventually have to be treated by cardiac transplantation or left ventricular assist device.

All first degree family members of the affected individual should be screened for ARVD. This is used to establish the pattern of inheritance. Screening should begin during the teenage years unless otherwise indicated. Screening tests include:

- Echocardiogram

- EKG

- Signal averaged EKG

- Holter monitoring

- Cardiac MRI

- Exercise stress test

Therapies that support reverse remodeling have been investigated, and this may suggests a new approach to the prognosis of cardiomyopathies (see ventricular remodeling).

Diastolic dysfunction must be differentiated from diastolic heart failure. Diastolic dysfunction can be found in elderly and apparently quite healthy patients. If diastolic dysfunction describes an abnormal mechanical property, diastolic heart failure describes a clinical syndrome. Mathematics describing the relationship between the ratio of Systole to Diastole in accepted terms of End Systolic Volume to End Diastolic Volume implies many mathematical solutions to forward and backward heart failure.

Criteria for diagnosis of diastolic dysfunction or diastolic heart failure remain imprecise. This has made it difficult to conduct valid clinical trials of treatments for diastolic heart failure. The problem is compounded by the fact that systolic and diastolic heart failure commonly coexist when patients present with many ischemic and nonischemic etiologies of heart failure. Narrowly defined, diastolic failure has often been defined as "heart failure with normal systolic function" (i.e. left ventricular ejection fraction of 60% or more). Chagasic heart disease may represent an optimal academic model of diastolic heart failure that spares systolic function.

A patient is said to have diastolic dysfunction if he has signs and symptoms of heart failure but the left ventricular ejection fraction is normal. A second approach is to use an elevated BNP level in the presence of normal ejection fraction to diagnose diastolic heart failure. Concordance of both volumetric and biochemical measurements and markers lends to even stronger terminology regarding scientific/mathematical expression of diastolic heart failure. These are both probably too broad a definition for diastolic heart failure, and this group of patients is more precisely described as having heart failure with normal systolic function. Echocardiography can be used to diagnose diastolic dysfunction but is a limited modality unless it is supplemented by stress imaging. MUGA imaging is an earlier mathematical attempt to distinguish systolic from diastolic heart failure.

No one single echocardiographic parameter can confirm a diagnosis of diastolic heart failure. Multiple echocardiographic parameters have been proposed as sufficiently sensitive and specific, including mitral inflow velocity patterns, pulmonary vein flow patterns, E:A reversal, tissue Doppler measurements, and M-mode echo measurements (i.e. of left atrial size). Algorithms have also been developed which combine multiple echocardiographic parameters to diagnose diastolic heart failure.

There are four basic Echocardiographic patterns of diastolic heart failure, which are graded I to IV:

- The mildest form is called an "abnormal relaxation pattern", or grade I diastolic dysfunction. On the mitral inflow Doppler echocardiogram, there is reversal of the normal E/A ratio. This pattern may develop normally with age in some patients, and many grade I patients will not have any clinical signs or symptoms of heart failure.

- Grade II diastolic dysfunction is called "pseudonormal filling dynamics". This is considered moderate diastolic dysfunction and is associated with elevated left atrial filling pressures. These patients more commonly have symptoms of heart failure, and many have left atrial enlargement due to the elevated pressures in the left heart.

Grade III and IV diastolic dysfunction are called "restrictive filling dynamics". These are both severe forms of diastolic dysfunction, and patients tend to have advanced heart failure symptoms:

- Class III diastolic dysfunction patients will demonstrate reversal of their diastolic abnormalities on echocardiogram when they perform the Valsalva maneuver. This is referred to as "reversible restrictive diastolic dysfunction".

- Class IV diastolic dysfunction patients will not demonstrate reversibility of their echocardiogram abnormalities, and are therefore said to suffer from "fixed restrictive diastolic dysfunction".

The presence of either class III and IV diastolic dysfunction is associated with a significantly worse prognosis. These patients will have left atrial enlargement, and many will have a reduced left ventricular ejection fraction that indicates a combination of systolic and diastolic dysfunction.

Imaged volumetric definition of systolic heart performance is commonly accepted as ejection fraction. Volumetric definition of the heart in systole was first described by Adolph Fick as cardiac output. Fick may be readily and inexpensively inverted to cardiac input and injection fraction to mathematically describe diastole. Decline of injection fraction paired with decline of E/A ratio seems a stronger argument in support of a mathematical definition of diastolic heart failure.

Another parameter to assess diastolic function is the , which is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E'). Diastolic dysfunction is assumed when the E/E' ratio exceed 15.

As an overall medical condition PVCs are normally not very harmful to patients that experience them, but frequent PVCs may put patients at increased risk of developing arrhythmias or cardiomyopathy, which can greatly impact the functioning of the heart over the span of that patient's life. On a more serious and severe scale, frequent PVCs can accompany underlying heart disease and lead to chaotic, dangerous heart rhythms and possibly sudden cardiac death.

Asymptomatic patients that do not have heart disease have long-term prognoses very similar to the general population, but asymptomatic patients that have ejection fractions greater than 40% have a 3.5% incidence of sustained ventricular tachycardia or cardiac arrest. One drawback comes from emerging data that suggests very frequent ventricular ectopy may be associated with cardiomyopathy through a mechanism thought to be similar to that of chronic right ventricular pacing associated cardiomyopathy. Patients that have underlying chronic structural heart disease and complex ectopy, mortality is significantly increased.

In meta-analysis of 11 studies, people with frequent PVC (≥1 time during a standard electrocardiographic recording or ≥30 times over a 1-hour recording) had risk of cardiac death 2 times higher than persons without frequent PVC. Although most studies made attempts to exclude high-risk subjects, such as those with histories of cardiovascular disease, they did not test participants for underlying structural heart disease.

In a study of 239 people with frequent PVCs (>1000 beats/day) and without structural heart disease (i.e. in the presence of normal heart function) there were no serious cardiac events through 5.6 years on average, but there was correlation between PVC prevalence and decrease of ejection fraction and increase of left ventricular diastolic dimension. In this study absence of heart of disease was excluded by echocardiography, cardiac magnetic resonance imaging in 63 persons and Holter monitoring.

Another study has suggested that in the absence of structural heart disease even frequent (> 60/h or 1/min) and complex PVCs are associated with a benign prognosis. It was study of 70 people followed by 6.5 years on average. Healthy status was confirmed by extensive noninvasive cardiologic examination, although cardiac catheterization of a subgroup disclosed serious coronary artery disease in 19%. Overall survival was better than expected.

On the other hand, the Framingham Heart Study reported that PVCs in apparently healthy people were associated with a twofold increase in the risk of all-cause mortality, myocardial infarction and cardiac death. In men with coronary heart disease and in women with or without coronary heart disease, complex or frequent arrhythmias were not associated with an increased risk. The at-risk people might have subclinical coronary disease. These Framingham results have been criticised for the lack of rigorous measures to exclude the potential confounder of underlying heart disease.

In the ARIC study of 14,783 people followed for 15 to 17 years those with detected PVC during 2 minute ECG, and without hypertension or diabetes on the beginning, had risk of stroke increased by 109%. Hypertension or diabetes, both risk factors for stroke, did not change significantly risk of stroke for people with PVC. It is possible that PVCs identified those at risk of stroke with blood pressure and impaired glucose tolerance on a continuum of risk below conventional diagnostic thresholds for hypertension and diabetes. Those in ARIC study with any PVC had risk of heart failure increased by 63% and were >2 times as likely to die due to coronary heart disease (CHD). Risk was also higher for people with or without baseline CHD.

In the Niigata study of 63,386 people with 10-year follow-up period those with PVC during a 10-second recording had risk of atrial fibrillation increased nearly 3 times independently from risk factors: age, male sex, body mass index, hypertension, systolic and diastolic blood pressure, and diabetes.

Reducing frequent PVC (>20%) by antiarrhythmic drugs or by catheter ablation significantly improves heart performance.

Recent studies have shown that those subjects who have an extremely high occurrence of PVCs (several thousand a day) can develop dilated cardiomyopathy. In these cases, if the PVCs are reduced or removed (for example, via ablation therapy) the cardiomyopathy usually regresses.

Also, PVCs can permanently cease without any treatment, in a material percentage of cases.

Investigation is tailored towards the symptoms and signs. A proper and detailed history looking for the occupational exposures, and for signs of conditions listed above is the first and probably the most important part of the workup in patients with interstitial lung disease. Pulmonary function tests usually show a restrictive defect with decreased diffusion capacity (DLCO).

A lung biopsy is required if the clinical history and imaging are not clearly suggestive of a specific diagnosis or malignancy cannot otherwise be ruled out. In cases where a lung biopsy is indicated, a trans-bronchial biopsy is usually unhelpful, and a surgical lung biopsy is often required.

Chest radiography is usually the first test to detect interstitial lung diseases, but the chest radiograph can be normal in up to 10% of patients, especially early on the disease process.

High resolution CT of the chest is the preferred modality, and differs from routine CT of the chest. Conventional (regular) CT chest examines 7–10 mm slices obtained

at 10 mm intervals; high resolution CT examines 1-1.5 mm slices at 10 mm

intervals using a high spatial frequency reconstruction algorithm. The HRCT therefore provides approximately 10 times more resolution than the conventional CT chest, allowing the HRCT to elicit details that cannot otherwise be visualized.

Radiologic appearance alone however is not adequate and should be interpreted in the clinical context, keeping in mind the temporal profile of the disease process.

Interstitial lung diseases can be classified according to radiologic patterns.

The differential diagnosis for berylliosis includes:

- Sarcoidosis

- Granulomatous lung diseases

- Tuberculosis

- Fungal infections

- Granulomatosis with polyangiitis

- Idiopathic pulmonary fibrosis

- Hypersensitivity pneumonitis

- Asthma

Of these possibilities, berylliosis presents most similarly to sarcoidosis. Some studies suggest that up to 6% of all cases of sarcoidosis are actually berylliosis.

Definitive diagnosis of berylliosis is based on history of beryllium exposures, documented beryllium sensitivity and granulomatous inflammation on lung biopsy. Given the invasive nature of a lung biopsy diagnosis can also be based on clinical history consistent with berylliosis, abnormal chest x-ray or CT scan findings, an abnormalities in pulmonary function tests.

Establishing beryllium sensitivity is the first step in diagnosis. The beryllium lymphocyte proliferation test (BeLPT) is the standard way of determining sensitivity to beryllium. The test is performed by acquiring either, peripheral blood or fluid from a bronchial alveolar lavage, and lymphocytes are cultured with beryllium sulfate. Cells are then counted and those with elevated number of cells are considered abnormal. Those exposed persons with two abnormal BeLPT tested with peripheral blood, or one abnormal and one borderline result, are considered beryllium sensitized. Also, those with one abnormal BeLPT tested with fluid from a bronchial alveolar lavage are considered sensitized.

Chest radiography findings of berylliosis are non-specific. Early in the disease radiography findings are usually normal. In later stages interstitial fibrosis, pleural irregularities, hilar lymphadenopathy and ground-glass opacities have been reported. Findings on CT are also not specific to berylliosis. Findings that are common in CT scans of people with berylliosis include parenchymal nodules in early stages. One study found that ground-glass opacities were more commonly seen on CT scan in berylliosis than in sarcoidosis. In later stages hilar lymphadenopathy, intersitial pulmonary fibrosis and pleural thickening.

Berylliosis is an occupational disease. Relevant occupations are those where beryllium is mined, processed or converted into metal alloys, or where machining of metals containing beryllium and recycling of scrap alloys occurs. It is associated with aerospace manufacturing, microwave semiconductor electronics, beryllium mining or manufacturing of fluorescent light bulbs (which once contained beryllium compounds in their internal phosphor coating). Beryllia was used in lamp manufacture because of ceramic's obvious virtues for insulation and heat resistance, and also because beryllia could be made transparent. Certain welding anodes along with other electrical contacts and even non-sparking tools are made of beryllium copper alloy and the subsequent machining of such materials would cause the disease as well.