Phrenic nerve palsy causing hemidiaphragm paralysis is a very uncommon feature of thoracic aortic aneurysm.

Thoracic aortic aneurysms are usually asymptomatic however chest pain is most commonly reported symptom. Left hemidiaphragm paralysis, because of left phrenic nerve palsy, is a very rare presentation of thoracic aortic aneurysm.
Thoracic aortic aneurysm may present atypical symptoms such as dysphagia due to compression of the oesophagus; hoarseness due to vocal cord paralysis or compression of the recurrent laryngeal nerve; superior vena cava syndrome due to compression of the superior vena cava; cough, dyspnoea or both due to tracheal compression; haemoptysis due to rupture of the aneurysm into a bronchus; and shock due to rupture of the aneurysm.
Common causes of phrenic nerve palsy include malignancy such as bronchogenic carcinoma, as well as mediastinal and neck tumours. Phrenic nerve palsy can also occur due to a penetrating injury or due to iatrogenic causes arising, for example, during cardiac surgery and central venous catheterization. Many cases or phrenic nerve palsy are idiopathic.

The chance of two carriers of a recessive gene having a child that is homozygous for that disease (that is both genes are transmitted to the child) is 25%. Therefore, the chances of this couple having a child with CF are 25%(1/4) x 1/20 = 1/80.

Acute epiglottitis is a life-threatening disorder with serious implications to the anaesthesiologist because of the potential for laryngospasm and irrevocable loss of the airway. There is inflammatory oedema of the arytenoids, aryepiglottic folds and the epiglottis; therefore, supraglottitis may be used instead or preferred to the term acute epiglottitis.

Acute epiglottitis can occur at any age. The responsible organism used to be Hemophilus influenzae type B (Hib), but infection with group A b-haemolytic Streptococci has become more frequent after the widespread use of Hemophilus influenzae vaccination.

The typical presentation in epiglottitis includes acute occurrence of high fever, severe sore throat and difficulty in swallowing with the sitting up and leaning forward position in order to enhance airflow. There is usually drooling because of difficulty and pain on swallowing. Acute epiglottitis usually leads to generalized toxaemia. The most common differential diagnosis is croup and a foreign body in the airway. A late referral to an acute care setting with its serious consequences may result from difficulty in differentiation between acute epiglottitis and less urgent causes of a sore throat, shortness of breath and dysphagia.

The normal partial pressure reference values are:
– PaO2 more than 80 mmHg (11 kPa)
– PaCO2 less than 45 mmHg (6.0 kPa).
This patient has an elevated PaCO2 (7.4kPa)
Hypoxemia (PaO2 <8kPa) with hypercapnia (PaCO2 >6.0kPa).
The pH is also lower than 7.35 at 7.3

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the build-up of carbon dioxide levels (PaCO2) that has been generated by the body but cannot be eliminated. The underlying causes include:
– Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)
– Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)
– A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)
– Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)
– Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive chronic lung disease. Typically, COPD includes emphysema and chronic bronchitis. COPD is characterized by the restriction of airflow into and out of the lungs. The obstruction of airflow makes breathing difficult. The causes of COPD include smoking, long-term exposure to air pollutants and a rare genetic disorder.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) developed the GOLD Staging System. In the GOLD System, the forced expiratory volume in one second (FEV1) measurement from a pulmonary function test is used to place COPD into stages. Often, doctors also consider your COPD symptoms.

COPD has four stages. The stages of COPD range from mild to very severe. COPD affects everyone differently. Because COPD is a progressive lung disease, it will worsen over time.
The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 63 which falls within the stage 2 or moderate COPD.

Serial Peak Expiratory Flow measurement at work and home is a feasible, sensitive, and specific test for the diagnosis of occupational asthma. For a diagnosis of occupational asthma, it is important to establish a relationship objectively between the workplace exposure and asthma symptoms and signs. Physiologically, this can be achieved by monitoring airflow limitation in relation to occupational exposure(s). If there is an effect of a specific workplace exposure, airflow limitation should be more prominent on work days compared with days away from work (or days away from the causative agent). Airflow limitation can be measured by spirometry, with peak expiratory flow (PEF) and/or forced expiratory volume in 1 s(FEV1) being the most useful for observing changes in airway calibre. Other tests mentioned are less reliable and would not help in establishing a satisfactory diagnosis of occupational asthma.

Type I pneumocyte: The cell responsible for the gas (oxygen and carbon dioxide) exchange that takes place in the alveoli. It is a very thin cell stretched over a very large area. This type of cell is susceptible to a large number of toxic insults and cannot replicate itself.
Type II pneumocyte: The cell responsible for the production and secretion of surfactant (the molecule that reduces the surface tension of pulmonary fluids and contributes to the elastic properties of the lungs). The type 2 pneumocyte is a smaller cell that can replicate in the alveoli and will replicate to replace damaged type 1 pneumocytes. Alveolar macrophages are the primary phagocytes of the innate immune system, clearing the air spaces of infectious, toxic, or allergic particles that have evaded the mechanical defences of the respiratory tract, such as the nasal passages, the glottis, and the mucociliary transport system. The main role of goblet cells is to secrete mucus in order to protect the mucous membranes where they are found. Goblet cells accomplish this by secreting mucins, large glycoproteins formed mostly by carbohydrates.

In adult practice, biochemical analysis of pleural fluid plays an important part in the management of pleural effusions. Protein levels or Light’s criteria differentiate exudates from transudates, while infection is indicated by pleural acidosis associated with raised LDH and low glucose levels. In terms of treatment, the pH may even guide the need for tube drainage, suggested by pH <7.2 in an infected effusion, although the absolute protein values are of no value in determining the likelihood of spontaneous resolution or chest drain requirements. pH is therefore the most important factor.

Classic clinical features associated with active pulmonary TB are as follows (elderly individuals with TB may not display typical signs and symptoms):
– Cough
– Weight loss/anorexia
– Fever
– Night sweats
– Haemoptysis
– Chest pain (can also result from tuberculous acute pericarditis)
– Fatigue

Test:
Acid-fast bacilli (AFB) smear and culture – Using sputum obtained from the patient.
AFB stain is quick but requires a very high organism load for positivity, as well as the expertise to read the stained sample. This test is more useful in patients with pulmonary disease.
Obtain a chest radiograph to evaluate for possible associated pulmonary findings. If chest radiography findings suggest TB and a sputum smear is positive for AFB, initiate treatment for TB.

Whilst asthma and COPD are different diseases they cause similar symptoms, which can present a challenge in identifying which of the two diseases a patient is suffering from. COPD causes chronic symptoms and narrowed airways which do not respond to treatment to open them up. In the case of asthma the constriction of the airways through inflammation tends to come and go and treatment to reduce inflammation and to open up the airways usually works well.

COPD is more likely than asthma to cause a chronic cough with phlegm and is rare before the age of 35 whilst asthma is common in under-35s. Disturbed sleep caused by breathlessness and wheeze is more likely in cases of asthma, as is a history of allergies, eczema and hay fever. Differentiating between COPD and asthma requires a history of both symptoms and spirometry. The spirometry history should include post bronchodilator measurements, the degree of reversibility and, ideally, home monitoring which gives a history of diurnal variation.

Airflow Obstruction: Both asthma and COPD are characterised by airflow obstruction. Airflow obstruction is defined as a reduced FEV1 and a reduced FEV1/FVC ratio, such that FEV1 is less than 80% of that predicted, and FEV1/FVC is less than 0.7.

These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

COPD: COPD is a chronic, slowly progressive disorder characterised by airflow obstruction (reduced FEV1 and FEV1/VC ratio) that does not change markedly over several months. The airflow obstruction is not fully reversible.

Spirometry COPD Asthma
VC Reduced Nearly normal
FEV1 Reduced Reduced in attack
FVC (or FEV6) Reduced Nearly normal
FEV1 Ratio
(of VC/FVC/FEV6) Reduced in attack

This man has a low FEV1 and FVC. His diffusions capacity is also low despite having a normal total lung capacity. These values confirm a diagnosis of COPD.

Postmenopausal oestrogen therapy and hormone therapy are associated with an increased risk of thromboembolism. The relative risk seems to be even greater if the treated population has pre-existing risk factors for thromboembolism, such as obesity, immobilization, and fracture. Cor pulmonale can occur secondary to small recurrent pulmonary embolisms. Pneumonias and bronchiectasis usually present with purulent sputum, and in case of carcinoma there may be other associated symptoms like weight loss, etc.

V/Q scanning carries a slightly increased risk of childhood cancer compared with CTPA – 1/280,000 versus less than 1/1,000,000 – but carries a lower risk of maternal breast cancer. The rest of the options are true.

Extrinsic allergic alveolitis (EAA) refers to a group of lung diseases that can develop after exposure to certain substances. The name describes the origin and the nature of these diseases:

‘extrinsic’ – caused by something originating outside the body
‘allergic’ – an abnormally increased (hypersensitive) body reaction to a common substance
‘alveolitis’ – inflammation in the small air sacs of the lungs (alveoli)

Symptoms can include: fever, cough, worsening breathlessness and weight loss. The diagnosis of the disease is based on a history of symptoms after exposure to the allergen and a range of clinical tests which usually includes: X-rays or CT scans, lung function and blood tests.

EAA is not a ‘new’ occupational respiratory disease and occupational causes include bacteria, fungi, animal proteins, plants and chemicals.

Examples of EAA include:

Farmer’s lung
This is probably the most common occupational form of EAA and is the outcome of an allergic response to a group of microbes, which form mould on vegetable matter in storage. During the handling of mouldy straw, hay or grain, particularly in a confined space such as a poorly ventilated building, inhalation of spores and other antigenic material is very likely.

There also appears to be a clear relationship between water content of crops, heating (through mould production) and microbial growth, and this would apply to various crops and vegetable matter, with the spores produced likely to cause EAA.

Farmer’s lung can be prevented by drying crops adequately before storage and by ensuring good ventilation during storage. Respiratory protection should also be worn by farm workers when handling stored crops, particularly if they have been stored damp or are likely to be mouldy.

Bronchial carcinoids are uncommon, slow growing, low-grade, malignant neoplasms, comprising 1-2% of all primary lung cancers.
It is believed to be derived from surface of bronchial glandular epithelium. Mostly located centrally, they produce symptoms and signs of bronchial obstruction such as localized wheeze, non resolving recurrent pneumonitis, cough, chest pain, and fever. Haemoptysis is present in approximately 50% of the cases due to their central origin and hypervascularity.
Central bronchial carcinoids are more common than the peripheral type and are seen as endobronchial nodules or hilar/perihilar mass closely related to the adjacent bronchus. Chest X-ray may not show the central lesion depending on how small it is.

Pneumothorax is defined as air in the pleural space and may be classified as spontaneous, traumatic or iatrogenic. Primary spontaneous pneumothorax occurs in patients without clinically apparent lung disease.
Primary pneumothorax has an incidence of 18-28 per 100,000 per year for men and 1.2-6 per 100,000 per year for women. Most patients present with ipsilateral pleuritic chest pain and acute shortness of breath. Shortness of breath is largely dependent on the size of the pneumothorax and whether there is underlying chronic lung disease.

Young patients may have chest pain only. Most episodes of pneumothorax occur at rest. Symptoms may resolve within 24 hours in patients with primary spontaneous pneumothorax. The diagnosis of a pneumothorax is confirmed by finding a visceral pleural line displaced from the chest wall, without distal lung markings, on a posterior-anterior chest radiograph.

Breathless patients should not be left without intervention regardless of the size of pneumothorax. If there is a rim of air >2cm on the chest X-ray, this should be aspirated.
Aspiration is successful in approximately 70 per cent of patients; the patient may be discharged subsequently. A further attempt at aspiration is recommended if the patient remains symptomatic and a volume of less than 2.5 litres has been aspirated on the first attempt.

If unsuccessful, an intercostal drain is inserted. This may be removed after 24 hours after full re-expansion or cessation of air leak without clamping and discharge may be considered.

The normal partial pressure reference values are: oxygen PaO2 more than 80 mmHg (11 kPa), and carbon dioxide PaCO2 lesser than 45 mmHg (6.0 kPa).
This patient has an elevated PaCO2 of 6.8kPa which exceeds the normal value of less than 6.0kPa.
The pH is also lower than 7.35 at 7.32

In any patient with asthma, an increasing PaCO2 indicates severe airway obstruction that is leading to respiratory muscle fatigue and patient exhaustion.

According to the British Thoracic Society guidelines:
Indications for admission to intensive care or high-dependency units include
patients requiring ventilatory support and those with acute severe or life-threatening asthma who are failing to respond to therapy, as evidenced by:
• deteriorating PEF
• persisting or worsening hypoxia
• hypercapnia
• arterial blood gas analysis showing fall in pH or rising hydrogen concentration
• exhaustion, feeble respiration
• drowsiness, confusion, altered conscious state
• respiratory arrest

Transfer to ICU accompanied by a doctor prepared to intubate if:
• Deteriorating PEF, worsening or persisting hypoxia, or hypercapnia
• Exhaustion, altered consciousness
• Poor respiratory effort or respiratory arrest

A single dose of intravenous magnesium sulphate is safe and may improve lung function and reduce intubation rates in patients with acute severe asthma. Intravenous magnesium sulphate may also reduce hospital admissions in adults with acute asthma who have had little or no response to standard treatment.

Consider giving a single dose of intravenous magnesium sulphate to
patients with acute severe asthma (PEF <50% best or predicted) who have not had a good initial response to inhaled bronchodilator therapy.
Magnesium sulphate (1.2–2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff.

An aspergilloma is a fungus ball (mycetoma) that develops in a pre-existing cavity in the lung parenchyma. Underlying causes of the cavitary disease may include treated tuberculosis or other necrotizing infection, sarcoidosis, cystic fibrosis, and emphysematous bullae. The ball of fungus may move within the cavity but does not invade the cavity wall. Aspergilloma may manifest as an asymptomatic radiographic abnormality in a patient with pre-existing cavitary lung disease due to sarcoidosis, tuberculosis, or other necrotizing pulmonary processes. In patients with HIV disease, aspergilloma may occur in cystic areas resulting from prior Pneumocystis jiroveci pneumonia. Of patients with aspergilloma, 40-60% experience haemoptysis, which may be massive and life threatening. Less commonly, aspergilloma may cause cough and fever.

Allergic bronchopulmonary aspergillosis (ABPA) is a form of lung disease that occurs in some people who are allergic to Aspergillus. With ABPA, this allergic reaction causes the immune system to overreact to Aspergillus leading to lung inflammation. ABPA causes bronchospasm (tightening of airway muscles) and mucus build-up resulting in coughing, breathing difficulty and airway obstruction.

Blood tests are used to look for signs of an allergic reaction. This includes evaluating your immunoglobulin E (IgE) level. This level is increased with any type of allergy. Many people with asthma have higher than normal IgE levels. In ABPA however, the IgE level is extremely high (more than 1000 ng/ml or 417 IU/ml). In addition to total IgE, all patients with ABPA have high levels of IgE that is specific to Aspergillus. A blood test can be done to measure specific IgE to Aspergillus. A blood or skin test for IgE antibodies to Aspergillus can be done to see if a person is sensitized (allergic) to this fungus. If these skin tests are negative (i.e. does not show a skin reaction) to Aspergillus fumigatus, the person usually does not have ABPA.
Therefore, there should be no change in medication since this patient does not have ABPA.

Sarcoidosis is an inflammatory disease that affects one or more organs but most commonly affects the lungs and lymph glands. The inflammation may change the normal structure and possibly the function of the affected organ(s).
The presentation in sarcoidosis varies with the extent and severity of organ involvement, as follows:
Asymptomatic (incidentally detected on chest imaging): Approximately 5% of cases.
Systemic complaints (fever, anorexia): 45% of cases
Pulmonary complaints (dyspnoea on exertion, cough, chest pain, and haemoptysis [rare]): 50% of cases

Löfgren syndrome (fever, bilateral hilar lymphadenopathy, and polyarthralgias): Common in Scandinavian patients, but uncommon in African-American and Japanese patients.

Dermatologic manifestations may include the following:
– Erythema nodosum
– A lower-extremity panniculitis with painful, erythematous nodules (often with Löfgren syndrome)
– Lupus pernio (the most specific associated cutaneous lesion)
– Violaceous rash on the cheeks or nose (common)
– Maculopapular plaques (uncommon)

Staging of sarcoidosis is as follows:
Stage 0: Normal chest radiographic findings
Stage I: Bilateral hilar lymphadenopathy
Stage II: Bilateral hilar lymphadenopathy and infiltrates
Stage III: Infiltrates alone
Stage IV: Fibrosis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for the treatment of arthralgias and other rheumatic complaints. Patients with stage I sarcoidosis often require only occasional treatment with NSAIDs.

Treatment in patients with pulmonary involvement is as follows:
Asymptomatic patients may not require treatment
In patients with minimal symptoms, serial re-evaluation is prudent
Treatment is indicated for patients with significant respiratory symptoms
Corticosteroids can produce small improvements in the functional vital capacity and in the radiographic appearance in patients with more severe stage II and III disease.

This patient has Stage 1 Sarcoidosis so observation is the most appropriate action.

Smoking cessation is the most effective intervention in stopping the progression of COPD, as well as increasing survival and reducing morbidity. This is why smoking cessation should be the top priority in the treatment of COPD. Long term oxygen therapy (LTOT) may increase survival in hypoxic patients. The rest of the options dilate airways, reduce inflammation and thereby improve symptoms but do not necessarily increase survival.

A study conducted showed that the average post smoking cessation weight gain was about 2 kg.
Withdrawal symptoms usually peak after 1–3 days and then decrease over a period of 3–4 weeks. After this time, the body has expelled most of the nicotine, and the withdrawal effects are mainly psychological.

Bronchiectasis is a long-term condition where the airways of the lungs become abnormally widened, leading to a build-up of excess mucus that can make the lungs more vulnerable to infection. The most common symptoms of bronchiectasis include:
– a persistent productive cough
– breathlessness.

The 3 most common causes in the UK are:
– a lung infection in the past, such as pneumonia or whooping cough, that damages the bronchi
– underlying problems with the immune system (the body’s defence against infection) that make the bronchi more vulnerable to damage from an infection
– allergic bronchopulmonary aspergillosis (ABPA) – an allergy to a certain type of fungi that can cause the bronchi to become inflamed if spores from the fungi are inhaled

Pulmonary metastasis is seen in 20-54% of extrathoracic malignancies. The lungs are the second most frequent site of metastases from extrathoracic malignancies. Twenty percent of metastatic disease is isolated to the lungs. The development of pulmonary metastases in patients with known malignancies indicates disseminated disease and places the patient in stage IV in TNM (tumour, node, metastasis) staging systems.
Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis in patients with known malignancies. Chest CT scanning without contrast is more sensitive than CXR.
Breast, colorectal, lung, kidney, head and neck, and uterus cancers are the most common primary tumours with lung metastasis at autopsy. Choriocarcinoma, osteosarcoma, testicular tumours, malignant melanoma, Ewing sarcoma, and thyroid cancer frequently metastasize to lung, but the frequency of these tumours is low.

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a coronavirus called SARS-associated coronavirus (SARS-CoV). SARS was first reported in Asia in February 2003.
In general, SARS begins with a high fever (temperature greater than 38.0°C). Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also have mild respiratory symptoms at the outset. About 10 to 20 percent of patients have diarrhoea. After 2 to 7 days, SARS patients may develop a dry cough. Most patients develop pneumonia. 

Salbutamol stimulates beta-2 adrenergic receptors, which are the predominant receptors in bronchial smooth muscle (beta-2 receptors are also present in the heart in a concentration between 10% and 50%).

Stimulation of beta-2 receptors leads to the activation of enzyme adenyl cyclase that forms cyclic AMP (adenosine-mono-phosphate) from ATP (adenosine-tri-phosphate). This increase of cyclic AMP relaxes bronchial smooth muscle and decrease airway resistance by lowering intracellular ionic calcium concentrations. Salbutamol relaxes the smooth muscles of airways, from trachea to terminal bronchioles.

Increased cyclic AMP concentrations also inhibits the release of bronchoconstrictor mediators such as histamine and leukotriene from the mast cells in the airway.

Carbon monoxide (CO) is a colourless, odourless gas produced by incomplete combustion of carbonaceous material. Clinical presentation in patients with CO poisoning ranges from headache and dizziness to coma and death. Hyperbaric oxygen therapy can significantly reduce the morbidity of CO poisoning, but a portion of survivors still suffer significant long-term neurologic and affective sequelae.

Complaints:
Malaise, flulike symptoms, fatigue
Dyspnoea on exertion
Chest pain, palpitations
Lethargy
Confusion
Depression
Impulsiveness
Distractibility
Hallucination, confabulation
Agitation
Nausea, vomiting, diarrhoea
Abdominal pain
Headache, drowsiness
Dizziness, weakness, confusion
Visual disturbance, syncope, seizure
Faecal and urinary incontinence
Memory and gait disturbances
Bizarre neurologic symptoms, coma

Vital signs may include the following:
Tachycardia
Hypertension or hypotension
Hyperthermia
Marked tachypnoea (rare; severe intoxication often associated with mild or no tachypnoea)
Although so-called cherry-red skin has traditionally been considered a sign of CO poisoning, it is in fact rare.

The clinical diagnosis of acute carbon monoxide (CO) poisoning should be confirmed by demonstrating an elevated level of carboxyhaemoglobin (HbCO). Either arterial or venous blood can be used for testing. Analysis of HbCO requires direct spectrophotometric measurement in specific blood gas analysers. Elevated CO levels of at least 3–4% in non-smokers and at least 10% in smokers are significant.

Studies have shown that benefits of Long-tern oxygen therapy (LTOT) include improved exercise tolerance, with improved walking distance, and ability to perform daily activities, reduction of secondary polycythaemia, improved sleep quality and reduced sympathetic outflow, with increased sodium and water excretion, leading to improvement in renal function.

Caplan’s syndrome is defined as the association between silicosis and rheumatoid arthritis (RA). It is rare and usually diagnosed in an advanced stage of RA. It generally affects patients with a prolonged exposure to silica.

Caplan’s syndrome presents with rheumatoid lung nodules and pneumoconiosis. Originally described in coal miners with progressive massive fibrosis, it may also occur in asbestosis, silicosis and other pneumoconiosis. Chest radiology shows multiple, round, well defined nodules, usually 0.5 – 2.0 cm in diameter, which may cavitate and resemble tuberculosis.

The vas deferens is a long tube that connects the epididymis to the ejaculatory ducts. It acts as a canal through which mature sperm may pass through the penis during ejaculation.

Most men with CF (97-98 percent) are infertile because of a blockage or absence of the vas deferens, known as congenital bilateral absence of the vas deferens (CBAVD). The sperm never makes it into the semen, making it impossible for them to reach and fertilize an egg through intercourse. The absence of sperm in the semen can also contribute to men with CF having thinner ejaculate and lower semen volume.

Idiopathic pulmonary fibrosis (IPF) is a condition in which the lungs become scarred and breathing becomes increasingly difficult.
The most common signs and symptoms of idiopathic pulmonary fibrosis are shortness of breath and a persistent dry, hacking cough. Many affected individuals also experience a loss of appetite and gradual weight loss.

The clinical findings of IPF are bibasilar reticular abnormalities, ground glass opacities, or diffuse nodular lesions on high-resolution computed tomography and abnormal pulmonary function studies that include evidence of restriction (reduced VC with an increase in FEV1/FVC ratio) and/or impaired gas exchange (increased P(A-a)O2 with rest or exercise or decreased diffusion capacity of the lung for carbon monoxide [DLCO]).