TS3 Pulmonary Function Testing Workshop

*The following objectives are identical to AM2Respiratory Pulmonary Function Tests

Required Readings:   Pagana,  Chap. 13; Dehn,  Chap. 13

Goals:             To successfully perform and/or interpret pulmonary function testing.

Objectives:

•        Identify spirometry as the most important common pulmonary function test (PFT) required for screening, assessing and managing most patients with respiratory disease seen in primary care.

Zen Seeker CMDT 2003 221

Spirometry is adequate for evaluation of most patients with suspected respiratory disease.  If airflow obstruction is evident, spirometry is repeated 10-20 minutes after an inhaled bronchodilator is administered.  This doubles the cost of the study.  The absence of improvement in spiorometry after inhaled bronchodilator in the pulmonary function laboratory does not preclude a successful clinical response to bronchodilator therapy.  Measurements of lung volumes and diffusion capacity are useful in selected patients, but these tests are expensive and should not be ordered routinely with spirometry.

                  Noble 177 http://home.mdconsult.com/das/book/body/0/959/122.html#P0177

Simple office spirometry evaluates basic flow rates (FEV₁ ) and forced vital capacity (FVC) and can document obstructive lung disease when FEV₁ /FVC is less than 70%. Full pulmonary function tests (PFTs), including measurement of the lung diffusing capacity for carbon monoxide (D_L CO), are necessary when spirometry is nondiagnostic.

                  656 http://home.mdconsult.com/das/book/body/0/959/506.html#P0656

Asthma

Increases in airway resistance associated with bronchial asthma can be readily detected by spirometry. Forced vital capacity (FVC) maneuvers reveal decreased flow rates, forced expiratory volume in 1 second (FEV₁ ) and peak expiratory flow rate (PEFR) are most often used to assess alterations in airway obstruction. It is common practice to determine responsiveness to bronchodilators during the evaluation of pulmonary function. Failure to document a response is not particularly helpful, however, since patients who show no improvement in the laboratory may respond outside the laboratory; a clinical trial of bronchodilator therapy should generally be given regardless of the laboratory response. It is important to assess the FEV₁ /FVC ratio, since a reduction of this ratio from expected values is specific for obstructive rather than restrictive disease. The severity of asthma can be judged on the basis of both pulmonary function studies and clinical presentation ( Table 72-1 ).

Noble online: Spirometry

•  in asthma, 656

•  in chronic obstructive pulmonary disease, 679, 680

•  in dyspnea, 177

•  in interstitial lung disease, 689

Jennyb Pagana p. 1072

Spirometry is the first test done in pulmonary function studies.  It used to measure air volumes in the lungs and can distinguish between obstructive and restrictive lung disease.  It is also used to manage disease states, by obtaining serial spirometries you can monitor the progression of the disease.

Anonymous

Pulmonary function tests are performed to detect abnormalities in respiratory function and to determine the extent of pulmonary abnormality. A spirometer is a machine that can measure air volumes. Pagana p. 1071

Spirometry alone does not establish the diagnosis of a specific disease. Spirometry does, however, aid in the differentiating pulmonary dysfunction as having an obstructive, restrictive, or mixed cause. Dehn p. 166

•        Define the following terms:

o       tidal volume

o       residual volume

o       vital capacity

o       total lung capacity

o       forced vital capacity (FVC)

o       FEV1

o       FEF 25-75%(maximal mid-expiratory flow rate)

Zen Seeker manual of diagnostic lab tests Pagana

tidal volume – (TV or V_T): volume of air inspired and expired with each normal respiration.

residual volume – (RV): volume of air remaining in the lungs following forced expiration.

vital capacity – (VC): maximal amount of air that can be expired after maximal inspiration.  VC=TV+IRV+ERV.

total lung capacity – (TLC): volume to which the lungs can be expanded with greatest inspiratory effort.  TLC=TV+IRV+ERV+RV.

forced vital capacity (FVC) – amount of air that can be forcefully expelled from a maximally inflated lung position.  Less than expected values occur in obstructive and restrictive pulmonary diseases.

Internet - Vital capacity measured with the subject exhaling as rapidly as possible; data relating volume, expiratory flow, and time form the basis for other pulmonary function tests, e.g., flow-volume curve, forced expiratory volume, forced expiratory time, forced expiratory flow.

FEV₁ – Forced expiratory volume in 1 second: volume of air expelled during the first second of FVC.  In obstructive pulmonary disease, airways are narrowed and resistance to flow is high.  Therefore not so much air can be expelled in 1 second, and FEV₁ is decreased because the amount of air originally inhaled is low, not because f airway resestance.  Therefore the FEV₁/FCV ratio shuld be measured.  In restrictive lung disease a normal value is 80%, and in obstructive lung disease this ratio is considerably less.  The FEV₁ value wil reliably improve with bronchodilator therapy if a spastic component to obstructive pulmonary disease exists.

FEF_25-75%  - rate of expired air between 200 mL and 120 mL during FVC (FEF –forced expiratory flow is the portion of air flow curve most affected by obstruction)

Internet

Lung Volume and Capacity:

Tidal volume (TV)

Inspiratory reserve volume (IRV)

Expiratory reserve volume (ERV)

Residual volume (RV)

Inspiratory capacity (IC) = TV+IRV

Vital capacity (VC) = TV+IRV+ERV

Functional residual capacity (FRC) =ERV+RV

Total lung capacity (TLC) =TV+IRV+ERV+RV = VC+RV

Dead space:

Dead space (V_D): The volume within the respiratory system that does not participate in gas exchange.

Anatomic dead space: The volume of gas contained in the conducting airways.

Alveolar dead space (pathological dead space)

= Anatomic dead space + alveolar dead space

V_E =V_T×f =(V_D+V_A) ×f = V_D+V_A

Jennyb pagana p. 1073

             Tidal Volume:  amt of air inspired AND expired with each normal resp.

            Residual volume:  amt of air remaining in the lungs after a forced exhalation. (air you can’t blow out)

            Vital capacity:  maximum amt of air that can be expired after a maximum inhalation

            Total lung capacity:  The volume to which your lungs can be expanded with a maximum inspiratory effort.  (The total amt of air you can breathe in and

                                              out plus the residual volume that stays in there all of the time)

            Forced vital capacity:  the amt of air that can be forcefully exhaled after a maximum inspiration

            FEV1:  the amt of air that is exhaled during a forced vital capacity in 1 second.

            FEF 25-75%:  The measured amt of air between 25-75% of the forced vital capacity.  The middle 50% of the exhalation is measured.

Anonymous Pagana p. 1072-1073

A. Tidal volume: (TV or V_t) Volume of air inspired and expired with each normal respiration.

B. Residual volume: (RV) Volume of air remaining in the lungs following a forced expiration.

C. Vital Capacity: (VC) Maximal amount of air that can be expired after maximal inspiration. VC = TV + IRV +ERV

D. Total lung capacity: (TLC) Volume to which the lungs can be expanded with greatest inspiratory effort. TLC = TV + IRV + ERV +RV

E. Forced vital capacity (FVC): Amount of air that can be forcefully expelled from a maximally inflated lung position. Less than expected values occur in obstructive and restrictive pulmonary disease.

F. Forced expiratory volume in one second FEV₁: Volume of air expelled during the first seconds of FVC.  In obstructive pulmonary disease, airways are narrowed and resistance to flow is high. Therefore not so much air can be expelled in 1 second, and FEV₁ is less than the predicted value. In restrictive lung disease, FEV₁ is decreased because the amount of air originally inhaled is low, not because of air way resistance.

G. FEF 25-75 % (maximal mid-expiratory flow rate): (MMEF) or (FEF) Maximal rate of air flow through the pulmonary tree during forced expiration. This test is independent of the patient’s efforts or cooperation. MMEF volumes are lower than expected in obstructive pulmonary disease and normal in restrictive pulmonary disease.

•        Describe the effects of obstructive pulmonary disease on flow rates, residual volume, and vital capacity.

Zen Lite Class

FEV₁ point at one second on volume/time graph

FVC point at 5 seconds on volume/time graph

If FEV₁/FVC <75% predicted - obstructive (don't bother trying to determine if it is restrictive)

If FVC is <80% predicted - restrictive

Zen Seeker Noble 679-680 http://home.mdconsult.com/das/book/body/0/959/525.html#top

• FEV₁ /FVC ratio below the subject's predicted value

• FEV₁ or FVC (less than 70%)

Pulmonary function testing (spirometry) is the only criterion standard to demonstrate an obstructive ventilatory defect, the hallmark of COPD.  An obstructive defect is defined by a FEV₁ /FVC ratio below the subject's predicted value. Alternatively, some pulmonary function laboratories use a percentage of FEV₁ or FVC (less than 70%) to define obstruction. Once airway obstruction has been documented from the FEV₁ /FVC ratio, the severity of the obstructive abnormality can be graded by the patient's percentage of predicted FEV₁:

• down to 70%, mild

• less than 70% to 60%, moderate

• less than 60% to 50%, moderately severe

• less than 50% to 34%, severe

• less than 34%, very severe

Patients with COPD have an irreversible obstructive impairment, as demonstrated by a persistently abnormal FEV₁ /FVC ratio, although the FEV₁ and FVC may vary between bouts of wheezing or pulmonary infection and clinical stability during optimal therapy. Any changes in spirometry, either improvement or worsening, should be viewed cautiously unless serial tests show a consistent trend. In contrast, asthmatic patients have a reversible obstructive impairment, with normalization of the FEV₁ /FVC ratio between clinical episodes of asthma. Spirometry can also be used to determine other parameters, such as the forced expiratory flow between the time 25% to 75% of the FVC is exhaled (FEF_25-75). A decrease in the FEF_25-75 is not used to diagnose an obstructive airways defect but does suggest obstruction of the small airways (less than 2 mm). Survival estimates of patients with COPD can be predicted based on the FEV₁ . The 5-year survival begins to decrease at a FEV₁ of 1.15 to 1.5 L. At ranges of FEV₁ of 0.75 to 1.15 L, 5-year survival decreases to 66% and is even lower in this group if chronic hypercapnia is present.

                  The functional ability of a patient with COPD is more precisely defined by a formal pulmonary exercise evaluation than by the FEV₁ alone. Functional impairment of patients with COPD varies for any given FEV₁ , although in general, functional ability decreases as the FEV₁ decreases. Exercise testing can also differentiate among limitations caused by gas exchange, ventilation, or cardiovascular abnormalities. Many patients with COPD are limited because of cardiovascular deconditioning and not by a gas exchange or ventilation impairment. An exercise test is not routinely recommended unless a major medical intervention is planned, for example, a lung resection in a patient when postoperative respiratory disability is a concern.

                  Spirometry in patients who demonstrate an obstructive defect typically includes measurement of the FEV₁ and FVC immediately after administration of an inhaled bronchodilator, the bronchodilator response. A widely used definition of a significant bronchodilator response is both a 12% increase and an absolute increase of 200 cc in the FEV₁ or FVC. Although not clinically proved, patients with a significant response are believed to derive the greatest benefit from inhaled bronchodilators and corticosteroids. The lack of a significant bronchodilator response, however, does not preclude clinical benefit, since the one-time administration of a bronchodilator during spirometry does not necessarily predict response with regular use. Therefore, inhaled bronchodilators should not be withheld from patients who do not exhibit a significant bronchodilator response. Some laboratories no longer perform a test of bronchodilator response in a patient with an established diagnosis of COPD, since the clinical practice is to prescribe a bronchodilator regardless of response. Finally, normalization of the FEV₁ /FVC percentage after administration of a bronchodilator strongly suggests asthma.

Jennyb pagana p. 1076

            Pts with obstructive lung disease have decreased air flow.  They can get the air in but it gets trapped in their floppy airways and they have a hard time getting it out.  So, their residual volume is increased secondary to trapped air, and their expiratory reserve volume is increased as well for the same reason.  Because of their increased RV, their vital capacity is decreased, and their flow is decreased i.e. FEV1, and FEF 25-75%.  Also their forced vital capacity is decreased as well. i.e. COPD

Anonymous

Obstructive disease reduces the ability of the lungs to move air, whereas lung volumes and capacities remain normal or increased. Abnormalities in air movement become most obvious by spirometry during forced expiration. As such, obstructive disease results in a decrease in the volume of air a patient is able to move during the first second (FEV₁) and midphase (FEV _{25% - 75%}) of forced expiration. Dehn p. 169

FEV₁ : Low

FVC: NL/Low

FEV₁/FVC: Low

VC: NL/Low

TLC: High

Dehn p. 170 Table 13-2

•        Define restrictive lung disease

Zen Seeker  Dehn 169-171

The pathologic presence of fibrotic tissue in the lungs underlies the basic cause of restrictive diseases.  As a result of pulmonary fibrosis, the lungs are stiffened, thus increasing the elastic recoil pressure with a reciprocal decrease in compliance.  The net effect is that restrictive disease prevents the lungs from expanding fully.

Disorders that result in restrictive lung dysfunction pattern

Fibrosis

Pneumonitis

Pneumoconiosis

Granulomatosis

Pulmonary edema

Neoplasm

Atelectasis

Pleural effusion or fibrosis

Kyphoscoliosis

Neuromuscular disease

Obesity

Abdominal distention

In pure restrictive disease, there is no obstruction to airflow.  Therefore, FEV₁ and other parameters of flow remain relatively normal.  Conversely, spirogram tracings from patients with restrictive disease reveal a decrease in lung volumes that may be identified by the forced vital capacity (FVC).

            Internet

Restrictive lung diseases are characterized by reduced lung volume, either because of an alteration in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus. In physiological terms, restrictive lung diseases are characterized by reduced total lung capacity (TLC), vital capacity, or resting lung volume. Accompanying characteristics are preserved airflow and normal airway resistance, which are measured as the functional residual capacity (FRC). If caused by parenchymal lung disease, restrictive lung disorders are accompanied by reduced gas transfer, which may be marked clinically by desaturation after exercise.

The many disorders that cause reduction or restriction of lung volumes may be divided into 2 groups based on anatomical structures.

The first is intrinsic lung diseases or diseases of the lung parenchyma. The diseases cause inflammation or scarring of the lung tissue (interstitial lung disease) or result in filling of the air spaces with exudate and debris (pneumonitis). These diseases can be characterized according to etiological factors. They include idiopathic fibrotic diseases, connective tissue diseases, drug-induced lung disease, and primary diseases of the lungs (including sarcoidosis).

The second is extrinsic disorders or extraparenchymal diseases. The chest wall, pleura, and respiratory muscles are the components of the respiratory pump, and they need to function normally for effective ventilation. Diseases of these structures result in lung restriction, impaired ventilatory function, and respiratory failure (e.g., nonmuscular diseases of the chest wall, neuromuscular disorders).

Jennyb pagana p. 1071

            Restrictive disease is the opposite of obstructive disease.  These pts have no problem getting the air out they can’t get the air in.  Inspiration is affected not exhalation.  Their ventilation is impaired secondary to inadequate chest expansion.  i.e. pulmonary fibrosis, tumors.

Anonymous Pagana p. 1071

Restrictive lung disease occurs when ventilation is disturbed by limitation of chest expansion. (e.g., pulmonary fibrosis, tumors, chest wall trauma). Inspiration is primarily affected.

•        Identify the subjective patient complaints that would make you include restrictive lung disease in your differential diagnosis.

Zen Seeker internet

• Symptoms of intrinsic diseases

• Progressive exertional dyspnea is the predominant symptom. Grading the level of dyspnea is useful as a method to gauge the severity of the disease and to follow its course.

• A dry cough is common and may be a disturbing sign. A productive cough is an unusual sign in most patients with diffuse parenchymal lung disorders.

• Hemoptysis or grossly bloody sputum occurs in patients with diffuse alveolar hemorrhage syndromes and vasculitis.

• Wheezing is an uncommon manifestation but can occur in patients with lymphangitic carcinomatosis, chronic eosinophilic pneumonia, and respiratory bronchiolitis.

• Chest pain is uncommon in most instances of the disease, but pleuritic chest pain can occur in patients with rheumatoid arthritis, systemic lupus erythematosus, and some drug-induced disorders.

• Symptoms of extrinsic disorders

• Nonmuscular diseases of the chest wall affect patients with kyphoscoliosis. Patients younger than 35 years tend to be asymptomatic, whereas middle-aged patients develop dyspnea, decreased exercise tolerance, and respiratory infections.

• The cause of respiratory failure is often multifactorial and is secondary to spinal deformity, muscle weakness, disordered ventilatory control, sleep disordered breathing, and airway disease.

• Neuromuscular disorders occur as the respiratory muscle weakness progresses. Patients develop dyspnea upon exertion, followed by dyspnea at rest, and their condition ultimately advances to respiratory failure.

• Patients with neuromuscular diseases develop significant respiratory muscle weakness and may demonstrate fatigue, dyspnea, impaired control of secretions, and recurrent lower respiratory tract infections. Acute and chronic respiratory failure, pulmonary hypertension, and cor pulmonale eventually ensue.

Jennyb pagana p. 1071 plus experience

            Pts with restrictive lung disease always complain of not being able to take a deep breath.  Their resp rate is increased to compensate.   Heart rate is usually elevated, and they are generally hypoxic with PO2’s < 60.  They have poor perfusion, and clubbing is usually present secondary to the low PO2’s.  They have increased SOB with activity, and CXray shows poor lung expansion.

Anonymous Current p. 238

Emphysema (Pink Puffer) : Major complaint is dyspnea, often severe, usually presenting after  age 50. Cough is rare, with scant clear, mucoid sputum. Patients are thin, with recent weight loss common. They appear uncomfortable, with evident use of accessory muscles of respiration. Chest is quiet without adventitious sounds. No peripheral edema.

•        Be able to describe and identify the spirometrey values and patterns that are consistent with restrictive lung disease.

Zen Lite Class

FEV₁ point at one second on volume/time graph

FVC point at 5 seconds on volume/time graph

If FEV₁/FVC <75% predicted - obstructive (don't bother trying to determine if it is restrictive)

If FVC is <80% predicted - restrictive

Zen Seeker  Dehn 170

Table 13-2  volumes and flows in Obstructive and Restrictive disease

http://asthma.about.com/cs/medicalreference/l/aa090897.htm

• 1 - Peak Expiratory Flow Rate (PEFR). The first landmark reached is the PEFR. The first blast of air exhaled from the patient reaches this flow rate almost immediately. The flow rate then quickly slows as more air is exhaled. This landmark is very important in judging if the patient is giving maximal effort, overall quality of the test, strength of expiratory muscles, and the condition of the large airways, such as the trachea and main bronchi. Asthmatics tend to have normal and decreased PEFRs.

   

• 2 - Forced Expiratory Flow at 25% of FVC (FEF25%). The FEF25% is the flow rate at the 25% point of the total volume (FVC) exhaled. Assuming maximal effort this flow rate is still indicative of the condition of fairly large to medium size bronchi. This landmark is used in calculations with the FEF75% to give FEF25-75%, the middle half of the FVC, which many physicians look at as not being dependent on patient effort and an indicator for obstruction in the small airways. This value is very dependent on the total volume exhaled (FVC) and tends to be highly variable from test to test. Asthmatics tend to have decreased FEF25%, the degree dependent on the amount of bronchoconstriction and inflammation of the airways. This is also true with all expiratory flow rates and expiratory flow rate calculations even if the patient is asymptomatic (without symptoms).

   

• 3 - Forced Expiratory Flow at 50% of FVC (FEF50%). The FEF50% is the flow rate at the 50% point of the total volume (FVC) exhaled. This landmark is at the midpoint of the FVC and indicates the status of medium to small airways, it's sometimes looked at instead of the FEF25-75%.

   

• 4 - Forced Expiratory Flow at 75% of FVC (FEF75%). The FEF75% is the flow rate at the 75% point of the total volume (FVC) exhaled. This landmark indicates the status of small airways and is used in the FEF25-75% calculation. Asthmatics, even if they are asymptomatic, typically show decreased FEF75% results. The damage done by most chronic pulmonary diseases show up in the smallest airways first and early indications of this damage begin to appear toward the end of the expiratory part of the Flow Volume Loop.

   

• 5 - Forced Inspiratory Flow at 25% of FVC (FIF25%). The FIF25% is the flow rate at the 25% point on the total volume inhaled. The inspiratory flow rates are relatively unimportant in assessing the asthmatic. Abnormalities here are indicators of upper airway obstructions. Areas of the mouth, upper and lower pharynx (back of the throat), larynx (voice box), and vocal-cords impact the inspiratory flow rates. Asthmatics tend to have normal inspiratory flow rate dependent on severity.

   

• 6 - Peak Inspiratory Flow Rate (PIFR). The fastest flow rate achieved during inspiration.

   

• 7 - Forced Inspiratory Flow at 50% of FVC (FIF50%). The FIF50% is the flow rate at the 50% point on the total volume inhaled.

   

• 8 - Forced Inspiratory Flow at 75% of FVC (FIF75%). The FIF75% is the flow rate at the 75% point on the total volume inhaled.

   

• 9 - Forced Expiratory Volume after 0.5 seconds (FEV0.5). The FEV0.5 indicates the amount of air exhaled with maximum effort in half a second. This test result is typically normal or reduced in asymptomatic asthmatics.

   

• 10 - Forced Expiratory Volume after 1 second (FEV1). The FEV1 indicates the amount of air exhaled with maximum effort in the first second.The FEV1 is another very important landmark in assessing the overall status of the patient and quality of the test. This test result is typically normal or reduced in asymptomatic asthmatics, and can be very reduced in symptomatic patients. This test result is also important in pre- and post-bronchodilator tests in determining the effects of bronchodilators on the airways. Asthmatic typically show improvements in FEV1 results after a bronchodilator is administered.

   

• 11 - Forced Expiratory Volume after 3 seconds (FEV3). The FEV3 indicates the amount of air exhaled with maximum effort in the first three seconds. This test result is typically normal or reduced in asymptomatic asthmatics

   

• 12 - Forced Vital Capacity (FVC). Another important result of a Flow Volume Loop is the FVC. Many of the other results depend on this number. The FVC is the total volume of air exhaled with maximal effort. Asthmatics can have FVCs greater than normal, normal, or less than normal depending on severity and presence of symptoms.

   

Some of the other numbers calculated from the Flow Volume Loop are:

• FEV0.5/FVC%, FEV1/FVC%, and FEV3/FVC% - These are ratios calculated by dividing the Forced Expiratory Volume results by the Forced Vital Capacity and expressed as a percentage of the FVC.

   

• FEF75-85% - Similar to the FEF25-75%, but it looks at the flow rates of the very small airways.

   

• FET25-75% - The time it takes to deliver the FEF25-75%.

   

• FET100% - The time it takes to exhale as much air as possible. Asthmatic typically take longer than normal due to airway obstruction and reduced flow rates.

   

There are other numbers that are calculated by combining results from Flow Volume Loops and other Pulmonary Function Tests. Some of these results are:

• Vmax 75, Vmax 50, Vmax 25 - These findings are similar to the FEF25%, FEF50%, and FEF75% but use the Total Lung Capacity instead of FVC. The difference being that Total Lung Capacity equals the FVC plus the Reserve Volume (RV). RV is the amount of air left in the lungs after you blow out as much as possible.

Anonymous Dehn p. 170 Table 13-2

FEV₁: NL

FVC: Low

FEV₁/FVC: NL/Low

VC: Low

TLC: Low

•        Identify the different groups of disorders that can cause restrictive lung disease according to “Overview of pulmonary function testing” by Paul L Enright, MD (handout).

Zen Seeker  UpToDate“ Overview of pulmonary function testing” by Paul L Enright

The many disorders which cause reduction of lung volumes (restriction) may be divided into three groups:

• Intrinsic lung diseases, which cause inflammation or scarring of the lung tissue (interstitial lung disease) or fill the airspaces with exudate or debris (acute pneumonitis).

• Extrinsic disorders, such as disorders of the chest wall or the pleura, which mechanically compress the lungs or limit their expansion.

• Neuromuscular disorders, which decrease the ability of the respiratory muscles to inflate and deflate the lungs.

Anonymous Dehn p. 169

Disorders Resulting in Restrictive Dysfunction

Fibrosis

Pneumonitis

Pneumonconiosis

Granulomatosis

Pulmonary edema

Neoplasm

Atalectasis

Pleural effusion or fibrosis

Kyphscoliosis

Neuromuscular disease

Obesity

Abdominal distention

•        Explain why the diffusion of carbon monoxide test (DLCO) will help differentiate between the different classes of restrictive disease.

Zen Seeker  UpToDate“ Overview of pulmonary function testing” by Paul L Enright

The DLCO is useful for differentiating intrinsic lung diseases, in which DLCO is generally reduced, from other causes of lung volume restriction, including neuromuscular disease or musculoskeletal deformity, in which DLCO is generally normal. (See "Diffusing capacity for carbon monoxide").

Changes in the DLCO are also useful for following the course of or response to therapy in patients with interstitial lung disease. Pulse oximetry during exercise is another test that can be useful in this setting, since oxygen saturation often falls during mild exercise in patients with interstitial lung disease [14]. (See "Approach to the adult with interstitial lung disease").

Anonymous Pagana p. 1072

Gas exchange studies measure the diffusing capacity of the lung (D_L), that is, the amount of gas exchange across the alveolar-capillary membrane per minute.  Most laboratories use carbon monoxide (CO) to measure D_L, because Co has a great affinity for hemoglobin and only a small concentration is needed. Because of this affinity of hemoglobin for Co, the only limiting factor to the transfer of the gas is its rate of diffusion across the alveolar-capillary membrane (which is what is measured). Gas exchange is abnormal in CHF, pneumonia, and other diseases that fill the alveoli with fluid or exudates. Any disease that causes deposition of material in the interstitium of the lung (e.g., ARDS, collagen vascular disease, Goodpasture’s syndrome, pulmonary fibrosis) will decrease gas exchange.

•        Given a patient’s history and PFT results that are consistent with a restrictive lung disease formulate:

o       a differential diagnosis

o       an appropriate physical examination

o       any further workup or referral

o       a plan for treatment or follow-up

Zen Seeker  Internet

Possible causes:

Fibrosis

Pneumonitis

Pneumoconiosis

Granulomatosis

Pulmonary edema

Neoplasm

Atelectasis

Pleural effusion or fibrosis

Kyphoscoliosis

Neuromuscular disease

Obesity

Abdominal distention

Differentials:

Acute Respiratory Distress Syndrome

Asbestosis

Chronic Bronchitis

Chronic Obstructive Pulmonary Disease

Coal Worker's Pneumoconiosis

Emphysema

Eosinophilic Pneumonia

Hypersensitivity Pneumonitis

Lung Transplantation

Lymphocytic Interstitial Pneumonia

Obesity

Pulmonary Eosinophilia

Pulmonary Fibrosis, Idiopathic

Pulmonary Fibrosis, Interstitial (Nonidiopathic)

Pulmonary Function Testing

Sarcoidosis

Silicosis

Physical Examination:

• Intrinsic disorders

• The physical examination in patients with intrinsic lung disorders may yield distinguishing physical findings.

• Those with chest wall disorders show obvious massive obesity and an abnormal configuration of the thoracic cage (eg, kyphoscoliosis, ankylosing spondylitis).

• Velcro crackles are common in most patients with interstitial lung disorders.

• Inspiratory squeaks or scattered, late, inspiratory high-pitched rhonchi are frequently heard in patients with bronchiolitis.

• Cyanosis at rest is uncommon in persons with interstitial lung diseases, and this is usually a late manifestation of advanced disease.

• Digital clubbing is common in those with IPF and is rare in others (eg, those with sarcoidosis or hypersensitivity pneumonitis).

• Extrapulmonary findings, including erythema nodosum, suggest sarcoidosis. A maculopapular rash can occur in those with connective tissue diseases, or it may be drug-induced. Raynaud phenomenon may be present in patients with connective tissue diseases, and telangiectasia is present in those with scleroderma. Peripheral lymphadenopathy, salivary gland enlargement, and hepatosplenomegaly are signs of systemic sarcoidosis. Uveitis may be observed in those with sarcoidosis and ankylosing spondylitis.

• Cor pulmonale occurs in the late stages of pulmonary fibrosis or advanced kyphoscoliosis. Pulmonary hypertension and cor pulmonale become evident when signs include a loud P2, right-sided precordial lift, and right-sided gallop.

• Extrinsic disorders

• By their very nature, severe kyphoscoliosis and massive obesity are easily recognizable. The pleural disorders are associated with decreased tactile fremitus, dullness upon percussion, and decreased intensity of breath sounds.

• In cases of neuromuscular diseases, the physical examination findings may indicate accessory muscles usage, rapid shallow breathing, paradoxical breathing, and other features of systemic involvement.

Further workup or referral:

Lab Studies:

•         Intrinsic lung diseases

o        Routine laboratory evaluations often fail to reveal positive findings. However, anemia can indicate vasculitis, polycythemia can indicate hypoxemia in advanced disease, and leukocytosis can suggest acute hypersensitivity pneumonitis.

o        The decision to perform additional tests should be directed by the findings of the clinical assessment. Antinuclear antibodies and rheumatoid factor should be measured to screen for collagen vascular disorders, creatine kinase for polymyositis, antineutrophilic cytoplasmic antibodies for vasculitis, and antiglomerular basement membrane antibody for Goodpasture syndrome.

o        The presence of precipitating antibodies to an antigen may help in diagnosing hypersensitivity pneumonitis. Serum angiotensin-converting enzyme levels are often elevated in patients with sarcoidosis, but this finding has poor specificity.

•         Extrinsic disorders: An elevated creatine kinase level may indicate myositis, which may cause muscle weakness and restrictive lung disease.

Imaging Studies:

•         Chest radiography for intrinsic lung disorders

o        The diagnosis of an interstitial lung disorder is often initially based on abnormal chest radiograph findings, which can be normal in as many as 10% of patients. All previous chest films should be reviewed.

o        The most common radiographic abnormality is a reticular pattern. Nodular, reticulonodular, or mixed patterns, such as alveolar filling (ie, ground-glass appearance), and increased interstitial markings are not unusual; however, these are not predictive of a specific pathological picture.

o        Air-space opacities suggest pulmonary hemorrhage, eosinophilic pneumonia, and BOOP.

o        Upper-zone predominance on chest radiographs is observed in patients with sarcoidosis, histiocytosis X, chronic hypersensitivity pneumonitis, pneumoconiosis, or ankylosing spondylitis. Lower-zone predominance is seen in patients with IPF, asbestosis, or collagen vascular diseases.

o        The finding of honeycombing correlates with advanced fibrosis and indicates a poor prognosis. Bilateral hilar lymphadenopathy, with or without mediastinal adenopathy, suggests sarcoidosis.

•         Computed tomography of the chest

o        High-resolution computed tomography of the chest can be helpful, but the accuracy of the findings for helping determine a specific etiology is inconsistent. Bibasilar peripheral lung zone involvement is seen in patients with IPF, asbestosis, connective tissue disease, or eosinophilic pneumonia.

o        Central disease along bronchovascular bundles is indicative of sarcoidosis or lymphangitic carcinoma.

o        Upper-zone predominance is observed in patients with sarcoidosis, eosinophilic granuloma, or chronic hypersensitivity pneumonitis. Lower-zone predominance is seen in patients with IPF, asbestosis, or rheumatoid arthritis.

o        Lower-zone and peripheral infiltration is ordinarily seen in patients with IPF or asbestosis.

o        The presence of bilateral cysts and nodules, with preservation of lung volumes, may suggest a diagnosis of LAM or histiocytosis X.

o        Bibasilar reticular fibrosis with coexisting retraction bronchiectasis indicates end-stage irreversible disease, and ground-glass attenuation may indicate the presence of an active inflammatory process with potential to respond to medical therapy.

•         Tests for extrinsic disorders

o        Evidence of nonmuscular diseases of the chest wall and associated deformities of the spinal column and ribs are readily appreciated on chest radiographs. The severity of kyphoscoliosis is determined by the Cobb angle, which, when greater than 100°, indicates severe deformity. Neuromuscular diseases are also diagnosed based on chest radiograph findings showing low volumes and basal atelectasis.

o        Fluoroscopy is used to assess for diaphragm paralysis.

o        A positive result from a sniff test may demonstrate paradoxical upward movement of the affected diaphragm.

Other Tests:

•         Pulmonary function testing

o        Complete lung function testing includes spirometry, lung volume, diffusing capacity, and arterial blood gas measurements. Pulmonary function test findings do not indicate a specific diagnosis or help distinguish alveolitis from fibrosis. Findings from sequential tests are invaluable for monitoring the course of the disease and assessing the response to therapy.

o        All disorders are associated with a restrictive defect with a reduction in TLC, FRC, and residual volume (RV).

o        While a reduction in the forced expiratory volume in one second (FEV₁) and the forced vital capacity (FVC) with a normal or increased FEV₁-to-FVC ratio suggests a restrictive pattern, the diagnosis of restriction is based on a decreased TLC. The assessment of the severity of restriction is also based on TLC.

o        An obstructive airflow limitation may be observed in patients with sarcoidosis, LAM, hypersensitivity pneumonitis, and pulmonary fibrosis with concomitant chronic obstructive pulmonary disease.

•         Tests for extrinsic lung disorders

o        In nonmuscular diseases of the chest wall, severe kyphoscoliosis produces a restrictive pattern. The TLC is markedly reduced, with relative preservation of the RV. The vital capacity is reduced, and the RV-to-TLC ratio is elevated. Chest wall components are reduced, and inspiratory muscle weakness may also contribute to the restrictive process. Maximal inspiratory and expiratory pressures are modestly decreased in patients with mild disease but are severely reduced in patients with advanced disease.

o        Hypoxemia is due to a ventilation-perfusion mismatch caused by the underlying atelectasis and shunt.

o        In neuromuscular diseases, the maximal inspiratory and expiratory mouth pressures vary from normal to severely reduced. When maximal inspiratory pressure falls below 30 cm of water, ventilatory failure commonly ensues.

o        Patients with chronic muscular diseases have a decreased vital capacity and FRC, but the RV is preserved. TLC is also moderately reduced. Breathing during sleep is often abnormal in these patients. They have nocturnal desaturation during rapid eye movement sleep, secondary to hypoventilation.

o        The diffusing capacity of lung for carbon monoxide (DLCO) is reduced in all patients with intrinsic lung disorders, and the severity of the reduction does not correlate well with the stage of the disease. The DLCO is the most sensitive parameter, and findings may be abnormal even when the lung volumes are preserved. A normal DLCO value excludes intrinsic lung disease and indicates a chest wall, pleural, or neuromuscular cause of restrictive lung disease.

o        Arterial blood gas values at rest may reveal hypoxemia. Arterial oxygen desaturation occurs with exercise, along with an excessive increase in the respiratory rate and a high ratio of dead-space gas volume to tidal gas volume.

o        Cardiopulmonary exercise testing with measurements of gas exchange and oxygenation is more sensitive, and findings correlate better with lung biopsy but do not help predict the prognosis. A 6-minute walk test with oximetry provides a measure of oxygen requirement and a quantifiable measure of disease progression.

Procedures:

•         Bronchoalveolar lavage

o        In selected cases, bronchoalveolar lavage (BAL) cellular analysis may be helpful to narrow the differential diagnosis. However, the utility of BAL in the clinical assessment and management of interstitial lung diseases remains to be established.

o        Performing BAL lymphocytosis in patients with IPF may help predict steroid responsiveness. A predominance of T lymphocytes with an elevated CD4-to-CD8 ratio is characteristic but not diagnostic of sarcoidosis.

o        BAL fluid may contain malignant cells, asbestos bodies, eosinophils, and hemosiderin macrophages, which assist in making a diagnosis.

•         Lung biopsy

o        A lung biopsy is not always required to make a diagnosis in patients suggested to have interstitial lung diseases. A lung biopsy can provide information that may help lead to a specific diagnosis, assess for disease activity, exclude neoplastic and infectious processes, establish a definitive diagnosis, and predict the prognosis.

o        Fiberoptic bronchoscopy with transbronchial lung biopsy is often the initial procedure of choice, especially when sarcoidosis, lymphangitic carcinomatosis, eosinophilic pneumonia, Goodpasture syndrome, histiocytosis X, hypersensitivity pneumonitis, or infection is suggested based on clinical evidence.

•         Surgical lung biopsy

o        Video-assisted thoracoscopic lung biopsy is the preferred method for obtaining lung tissue samples for analysis.

o        Histologic patterns may be helpful in narrowing the differential diagnosis. Honeycombing is seen in end-stage disease, in which the original disease process often cannot be differentiated.

•         The common histologic patterns include interstitial pneumonitis (ie, IPF). Subpleural and paraseptal inflammation is present, with an appearance of temporal heterogeneity. Patchy scarring of the lung parenchyma and normal, or nearly normal, alveoli interspersed between fibrotic areas is the hallmark of this disease. Also, the lung architecture is completely destroyed.

•         Desquamative interstitial pneumonitis is characterized by diffuse and temporally uniform involvement of the lung parenchyma. The alveoli are filled with macrophages and hyperplastic type II pneumocytes.

•         BOOP (also called proliferative bronchiolitis) is often patchy and peribronchiolar. The proliferation of granulation tissue within small airways and alveolar ducts is excessive and is associated with chronic inflammation of surrounding alveoli.

•         Diffuse alveolar damage is marked by a nonspecific reaction with diffuse temporally uniform involvement and marked thickening of the alveolar septa; inflammatory cell infiltration and type II cell hyperplasia and fibroblast proliferation are present.

•         For acute interstitial pneumonia, the pathological appearance is identical to that of diffuse alveolar damage.

•         In eosinophilic pneumonia, the eosinophils and macrophages are the predominant alveolar inflammatory cells, and they also extend into the interstitium.

•         Lymphocytic interstitial pneumonitis marked by a lymphoid infiltrate that involves both the interstitium and alveolar spaces is the prominent finding.

•         In nonspecific interstitial pneumonia, the lesions are characterized by a relatively uniform appearance consisting of mononuclear interstitial infiltrates associated with varying degrees of interstitial fibrosis.

•         Granulomatous lung diseases are marked by granulomas characterized by the accumulation of T lymphocytes, macrophages, and epithelioid cells. These may progress to pulmonary fibrosis.

Plan for treatment or follow-up:

Treatment depends on the specific diagnosis, which is based on findings from the clinical evaluation, imaging studies, and lung biopsy.

Corticosteroids, immunosuppressive agents, and cytotoxic agents are the mainstay of therapy for many of the interstitial lung diseases. Objective data assessing the risks and benefits of immunosuppressive and cytotoxic agents to treat diverse interstitial lung disorders are sparse. Direct comparisons among these agents are lacking.

Ancillary therapies include supplemental oxygen therapy, which alleviates exercise-induced hypoxemia and improves performance.

•         Idiopathic pulmonary fibrosis

o        The rate of progression of IPF is highly variable, and controversy exists regarding the timing of treatment. The disease may be responsive to treatment in the early, so-called inflammatory stage. IPF always progresses insidiously, and documenting the changes over short periods is difficult. Initiate a trial of therapy for 6-12 weeks, starting as early as possible, with the hope of slowing disease progression. Discontinue therapy if no benefit is observed or if adverse effects develop.

o        The prognosis for patients with IPF who do not respond to medical therapy is poor. They usually die within 2-3 years. These and other patients with severe functional impairment, oxygen dependency, and a deteriorating course should be listed for lung transplantation

•         Corticosteroids

o        Corticosteroids are a first-line therapy but are associated with myriad adverse effects. Corticosteroids, the most commonly used drugs, halt or slow the progression of pulmonary parenchymal fibrosis with variable success.

o        Questions about which patients should be treated, when therapy should be started, and what constitutes the best therapy receive uncertain answers at present.

o        Although subjectively most patients with IPF feel better, an objective improvement occurs in 20-30% patients. A favorable response is a reduction in symptoms; the clearing of radiographs; and improvements in FVC, TLC, and DLCO. The optimal duration of therapy is not known, but treatment for 1-2 years is suggested.

•         Cytotoxic therapy

o        Immunosuppressive cytotoxic agents may be considered for patients who do not respond to steroids, experience adverse effects, or have contraindications to high-dose corticosteroid therapy. The failure of steroid therapy is defined as a fall in FVC or TLC by 10%, a worsened radiographic appearance, and a decreased gas exchange at rest or with exercise.

o        Azathioprine is less toxic than methotrexate or cyclophosphamide and may be preferred as a corticosteroid-sparing agent for disorders that are not life threatening. A response to therapy may not occur for 3-6 months.

o        Because of potentially serious toxicities, cyclophosphamide is reserved for fulminant or severe inflammatory disorders refractory to alternate therapy.

•         Antifibrotic therapies

o        These therapies, including colchicine, are suggested for a variety of fibrotic disorders, including IPF.

o        Recent studies demonstrate no difference in the decline of pulmonary function with either colchicine or prednisone; therefore, a trial of therapy with colchicine is reasonable in less symptomatic patients or those who are experiencing adverse effects with steroid therapy.

•         Collagen vascular disease

o        Therapy for pulmonary fibrosis associated with collagen vascular disease is controversial because the course may be indolent. Because these diseases begin as an alveolitis, an aggressive approach may be warranted.

o        Patients with severe disease or those who have a deteriorating course must be treated with corticosteroids, cytotoxic therapy, or both.

•         Sarcoidosis

o        Because the disease remits spontaneously, patients with respiratory symptoms and radiographic or pulmonary function evidence of extensive disease may benefit from corticosteroids. Patients with hypercalcemia or extrapulmonary involvement generally require treatment. Therapy should be continued for 6 months or longer; however, even after prolonged treatment, up to 50% of patients relapse after therapy is discontinued.

o        For patients who do not respond to corticosteroids, alternate therapies (eg, chloroquine, methotrexate, azathioprine) may be used; however, data are limited.

•         Treatment of extrinsic lung disorders

o        Patients with nonmuscular chest wall disorders and neuromuscular disease may develop problems with ventilation and gas exchange during sleep. The effect of decreased chest wall and lung compliance or decreased muscle strength is hypercapnia and hypoxemia, which occurs initially during sleep. Identify and treat the cause of muscle weakness.

o        Treatment of neuromuscular diseases includes preventive therapies to minimize the impact of impaired secretion clearance and the prevention and prompt treatment of respiratory infections.

o        The patients who develop respiratory failure or have severe gas exchange abnormalities during sleep may be treated with noninvasive positive-pressure ventilation via a nasal or oronasal mask. Patients in whom these devices fail may require a permanent tracheotomy and ventilator assistance with a portable ventilator.

o        Noninvasive ventilation with body-wrap ventilators or positive-pressure ventilation has been proven beneficial because it helps relieve dyspnea and pulmonary hypertension and helps improve RV and gas exchange. Also, hospitalization rates are markedly reduced and the activities of daily living are enhanced.

o        Treatment for massive obesity consists of weight loss, which causes dramatic improvement in pulmonary function test findings but is harder to achieve. These patients require polysomnographic study because of the high incidence of nocturnal hypoventilation or upper airway obstructions. Either continuous positive airway pressure or noninvasive pressure ventilation helps correct hypoventilation and upper airway obstruction.

o        In advanced disease, when respiratory failure develops, these patients are treated with mechanical ventilation. If they have copious secretions, cannot control their upper airway, or are not cooperative, then invasive ventilation with a tracheotomy tube is indicated. In other patients, eg, those who have good airway control and minimal secretions, use noninvasive ventilation, initially nocturnal, and then intermittently.

Consultations:

•         Consultation with a pulmonologist is helpful for diagnosis and management.

Deterrence/Prevention:

•         Because the etiology of IPF is not known, prevention currently is not feasible. Several risk factors are known (eg, occupational metal or wood exposure and some common drugs have been identified); therefore, avoiding these may be prudent but is not proven.

Prognosis:

•         The natural history of interstitial lung diseases is variable. It depends on the specific diagnosis and the extent and severity of lung involvement. IPF is typically a relentless progressive disorder, and patients have a mean survival of 4-6 years after diagnosis.

•         Pulmonary sarcoidosis has a relatively benign self-limiting course, with spontaneous recovery or stabilization in most cases. Approximately 15% of patients develop pulmonary fibrosis and disability.

•         Prognosis for collagen vascular diseases, eosinophilic pneumonia, BOOP, and drug-induced lung disease is generally favorable with treatment.

•         Patients with chest wall diseases and neuromuscular disorders develop progressive respiratory failure and succumb during an intercurrent pulmonary infection.

Anonymous

A.  A differential diagnosis: Look at number 7 including Emphysema

B.  An appropriate physical examination: Check appropriate body systems that come with complaints.

C. Any further workup or referral: ABGs, Chest x-ray, Pulse Ox, Rule out what you thin maybe causing the complaint.

D. A plan for treatment or follow-up: Depends on the final diagnosis.