Believing that a significant bronchodilator response on PFTs equals a diagnosis of asthma

Obtaining pulmonary function testing (PFT) during an acute illness involving cardiopulmonary disease

Not commenting on, or working up, a DLCO decrease out of proportion to the degree of obstruction (often indicative of additional disease)

Believing that the DLCO is an assay for pulmonary capillary interstitial thickening (only)

The primary role for PFTs is to determine if abnormal lung function is present, and if so, is it significant enough to explain an individuals exercise limitation

There are three major types of pulmonary pathophysiologic malfunction that are screened for by PFT: obstructive physiology, restrictive physiology, and pulmonary vascular disease:

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  Spirometry screens for obstructive physiology

  
  
  
  
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    Obstructive disease limits exercise by causing a prolonged exhalation, which limits the individual’s ability to increase his or her minute volume (MV)

    
    
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    An inability to increase MV limits exercise as symptomatic lactic acidosis ensues instead of appropriate respiratory compensation

  
  
  
  
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  Lung volumes screen for restrictive physiology

  
  
  
  
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    Restrictive disease associated with parenchymal lung disease (DPLD) limits exercise by increasing the work of breathing (small, stiff lungs are more work to inflate) and by profound exercise-induced oxygen desaturation (as diffusion is severely limited by interstitial fibrosis or alveolar filling)

  
  
  
  
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  A DLCO measurement screens for pulmonary vascular disease and interstitial lung disease

  
  
  
  
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    Pulmonary vascular disease limits exercise by increasing dead space (vascular obstruction creates physiologic dead space) and by right ventricular (RV) afterload, which limits RV cardiac output (CO) and thus left ventricular (LV) CO

  
  

PFTs are also used to determine the severity of lung disease, where the:

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  Obstructive defect is based on the FEV1 % predicted

  
  
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  Restrictive Defect, is based on the TLC % predicted

PFTs are also essential in the assessment of lung resection tolerability for individuals with early-stage lung cancer (see lung cancer chapter)

Serial PFT measurements may be used to screen for:

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  Pulmonary drug toxicity (eg, amiodarone, biologics)

  
  
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  Progression of DPLD

  
  
  
  
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    Total lung capacity (TLC), forced vital capacity (FVC) and DLCO are relatively sensitive measures of disease progression

  
  
  
  
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  Progression of neuromuscular disease

Serial PFT measurements in individuals with asthma are useful to:

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  Demonstrate disease control (ie, normal PFTs)

  
  
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  Screen for the transition from reversible to fixed obstruction (eg, loss of a previously demonstrated bronchodilator response)

  
  
  
  
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    Which may prompt escalating therapy (eg, biologics)

  
  

Serial PFT measurements are much less useful in the management of chronic obstructive pulmonary disease (COPD)

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  Relegated to ensuring that worsening exercise limitation is attributable to declining lung function and not a new problem (eg, angina)

Spirometry involves measuring airflow and lung volume while the subject forcefully exhales from TLC to residual volume, otherwise known as a forced vital capacity maneuver ( Fig. 3.1 ).

Classic spirometry tracing showing volume over time during normal tidal breathing, followed by maximum exhalation and inhalation, with the key volumes and capacities (sums of volumes) labeled.

During forced expiration from TLC, normal airflow is almost immediately limited in the medium-sized airways by dynamic airway compression and collapse ( Fig. 3.2 )

Three different flow volume loops (showing exhalation limb only) from the same subject, with varying degrees of effort, illustrating how the peak flow rate is effort dependent. Schematic drawing of the medium-sized airway in cross section, embedded in a lattice of normal alveolar tissue, depicting the airway open at the onset of forced expiration (ie, approaching peak flow). Almost immediately, as lung volume drops from total lung capacity (TLC), the flow rate begins to decline, as positive intrathoracic pressure causes dynamic airway collapse (represented schematically by the medium-sized airway, collapsing, despite being embedded in a lattice of normal alveolar tissue). This decline in flow rate for a given lung volume is a function of the mechanical properties of the lung (ie, elastic recoil airway resistance) and is thus effort independent. Note how all three loops ultimately converge.

Dynamic airway collapse is:

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  Provoked by positive intrathoracic pressure generated during forced exhalation, which exerts a compressive force on intrathoracic structures (including medium-sized airways)

  
  
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  Resisted by the radial traction provided to the walls of the medium-sized airways by surrounding alveolar tissue (elastic recoil)

  
  
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  Responsible for the normal airway resistance encountered during forced expiration leading to the sloping nature of the exhalation limb of a normal flow volume loop

  
  
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  Effort independent, being a phenomenon of the elastic recoil properties of the lung at any given lung volume

  
  
  
  
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    As the lung deflates, its elastic recoil force decreases such that at a certain lung volume, positive intrathoracic pressure normally provokes dynamic collapse limiting airflow (normally at a low lung volume near complete exhalation)

    
    
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    Obstructive lung physiology occurs when dynamic collapse occurs early, limiting airflow at a relatively high lung volume

  
  

In patients with COPD/emphysema, loss of alveolar tissue leads to decreased radial traction, increasing the tendency of the medium-sized airways to collapse pathologically early during exhalation (at relatively high lung volumes), leading to a scooped exhalation limb of the obstructed flow volume loop

In patients with asthma, the medium-sized airway lumen is narrowed by airway tone and inflammation, leading to a similar premature (for a given lung volume) pathologic dynamic collapse

Importantly, the inspiratory limb of the flow volume loop appears as a uniform arc (in normal and emphysematous individuals alike), as the negative thoracic pressure of inspiration exerts an opening force on intrathoracic structures (including medium-sized airways), minimizing airway resistance ( Fig. 3.3 )

Normal flow volume loop on the left, with a schematic insert depicting a medium-sized airway, embedded in normal alveolar tissue, providing radial traction resisting airway collapse until the end of exhalation when lung volume is low. The flow volume loop on the right demonstrates a severe obstructive defect, with a schematic insert depicting a medium-sized airway prone to premature collapse at the beginning of exhalation when lung volume is still high, secondary to decreased radial traction.

With normal pulmonary mechanics, most of the air is exhaled from the lung in the first second

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  Said another way, the ratio of the forced expiratory volume in 1 second (FEV ₁ ) to the total forced volume exhaled, or forced vital capacity (FVC), should be high

  
  
  
  
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    The FEV ₁ /FVC should be > 70% (ratio of volumes, not percent)

  
  

In obstructive lung disease, dynamic airway collapse occurs pathologically early during exhalation, reducing airflow prematurely and increasing exhalation time

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  Said another way, the ratio of the FEV ₁ to the FVC (ie, total forced volume exhaled) should be low

  
  
  
  
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    The ratio of FEV ₁ to the FVC will be < 70%

  
  

This ratio of airflow for a given lung volume is a function of pulmonary mechanics (ie, airway resistance and elastic recoil) and is thus effort independent, making the FEV ₁ /FVC ratio superior to peak flow measurements in the determination of obstructive lung disease

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  Although the peak airflow rate will be reduced in obstructive lung disease, it is an effort-dependent measure, making it less reliable (see Fig. 3.2 )

A proportionate reduction in FVC and FEV1 with a preserved ratio (ie, FEV1/FVC> 70%) suggests a restrictive defect vs poor effort

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  TLC measurement required to confirm the diagnosis of a restrictive physiology

If lung volumes are not attainable, spirometry may strongly suggest a restrictive defect secondary to pulmonary fibrosis when the FVC is < 80% predicted and the FEV ₁ /FVC ratio is pathologically high (ie, > 115% predicted), implying increased elastic recoil, as occurs when areas of fibrosis stent open the medium sized airways, resisting normal dynamic airway collapse

The flow volume loop provides a visual representation of airflow during inhalation and exhalation

Although the inspiratory limb of the flow volume loop appears similar (as an arc) in most normal individuals, the shape of the expiratory slope demonstrates more variability as a function of individual effort and pulmonary mechanics ( Fig. 3.4 )

Several normal flow volume loops showing the wide range of shapes based on effort and individual lung mechanics.

Inspection of the flow volume loop is necessary to screen for obstruction of the large airways, as can occur in the setting of upper airway tumors, tracheal tumors, mediastinal masses (via external compression), subglottic stenosis, vocal cord paralysis/impingement, and tracheomalacia

Variable extrathoracic obstruction

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  Commonly caused by squamous cell cancers involving the larynx, subglottic stenosis, and vocal cord paralysis (as occurs as a complication of intubation or tracheostomy)

  
  
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  Variable obstruction of the upper extrathoracic portion of the airway leads to a flow limitation on inhalation only

  
  
  
  
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    This causes the normal arc of the inspiratory limb to be cut like an upside down plateau

    
    
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    Because the flow limitation is only present during inhalation (when negative intrathoracic pressure exerts a collapsing force on the extrathoracic airway), it is called variable extrathoracic obstruction ( Fig. 3.5A )

    
    
    
    
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      During exhalation, positive intrathoracic pressure exerts an opening force on the extrathoracic airway such that expiratory flow is not affected

    
    

    
    

    
    

    

    
    

    
    

    Schematic representation paired with idealized flow volume loops illustrating the flow limitation patterns of large airway obstruction. (A) Variable extrathoracic obstruction. Schematic representation of extrathoracic airway narrowing, with an anticipated flow volume loop below showing pathologic inspiratory flow limitation. (B) Variable intrathoracic airway obstruction. Schematic representation of intrathoracic airway narrowing, with an anticipated flow volume loop below showing pathologic expiratory flow limitation. (C) Fixed intrathoracic or extrathoracic obstruction. Schematic representation of a fixed airway narrowing spanning the intrathoracic and extrathoracic airway, with an anticipated flow volume loop below, showing pathologic inspiratory and expiratory flow limitation.

    
    
    
    
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    It is common for subjects to volitionally limit airflow (at their mouths) during the slow inspiratory vital capacity (VC) maneuver that generates the inspiratory limb of the flow volume loop

    
    
    
    
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      Because of this, a flow limitation should be evident on multiple trials to raise concern for upper airway obstruction

      
      
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      Additionally, some individuals experience a paradoxical vocal cord closure during the inspiratory maneuver (producing audible stridor), which they can often be “coached” out of by the PFT technician

    
    

  
  

Variable intrathoracic obstruction

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  Commonly caused by squamous cell tumors of the trachea, tracheomalacia, and external compression from mediastinal tumors/adenopathy

  
  
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  Variable obstruction of the intrathoracic portion of trachea leads to a flow limitation during exhalation only

  
  
  
  
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    This causes the normal sloped exhalation limb to be cut, as peak flow plateaus until lung volume is low enough that dynamic airway collapse supervenes and limits the remainder of the expiratory flow

    
    
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    Because the flow limitation is only present during forced exhalation (when positive intrathoracic pressure exerts a collapsing force on the intrathoracic airway), it is called variable intrathoracic obstruction ( Fig. 3.5B )

    
    
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    During inhalation, negative intrathoracic pressure exerts an opening force on the intrathoracic airway such that inspiratory flow is not affected

  
  

Fixed intrathoracic or extrathoracic obstruction

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  Commonly caused by squamous cell tumors of the trachea and the larynx (extending down into the thorax), or by a fixed narrowing anywhere in the main airway, commonly from tumor or scarring

  
  
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  Fixed obstruction of either the intrathoracic and extrathoracic airway leads to flow limitation during inhalation and exhalation

  
  
  
  
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    This causes the flow volume loop to appear ovoid as both inspiratory and expiratory limbs demonstrate plateauing of airflow

    
    
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    Because the airway obstruction does not vary normally with inspiration or expiration, it is called fixed intrathoracic-extrathoracic obstruction ( Fig. 3.5C )

  
  

Though not used for diagnosis, the flow volume loops of obstructive disease, restrictive disease, and mixed obstructive restrictive disease have a characteristic appearance ( Fig. 3.6 )

Flow volume loops illustrating classic disease patterns. (A) Mild obstructive disease, with a positive bronchodilator response (red loop). Notice the improvement in the scooped appearance of the expiratory limb after bronchodilator administration. (B) Moderate obstruction. (C) Severe obstruction. Note the y- axis scale difference. (D) Severe restriction. Note the A shape to the flow volume loop, created by the pathologically fast flows during exhalation as the increased elastic recoil of fibrosis resists dynamic airway collapse despite forced exhalation. (E) Mixed obstructive restrictive disease appearing as a combination of a restricted loop and an obstructed loop.

Measuring lung volume dynamically, by spirometry (ie, FVC), has one major limitation

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  If the patient has obstructive disease with air trapping, his or her RV will be increased

  
  
  
  
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    As the RV increases, it reduces the available space for ventilation (despite TLC increase, because there is limited space in the thorax), decreasing the VC

    
    
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    This is known as pseudorestriction

  
  

Pseudorestriction (secondary to obstructive lung disease) can only be distinguished from obstructive disease with concomitant restriction (aka mixed obstructive-restrictive disease), by measuring the TLC

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  TLC = the vital capacity (easy to measure via spirometry) + the residual volume (requires body plethysmography or the helium dilution technique)

Measuring TLC by helium dilution and body plethysmography

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  The helium dilution technique takes advantage of the fact that helium is not absorbed by the blood:

  
  
  
  
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    The subject breathes helium from a reservoir with a known amount of helium, effectively diluting the helium from the reservoir

    
    
    
    
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      Amount of helium in the reservoir = concentration of helium (C ₁ ) × volume of gas (V ₁ )

    
    
    
    
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    After several breaths the helium equilibrates between the reservoir and the lung, leading to a new, reduced concentration of helium in the reservoir (C ₂ )

    
    
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    The change in concentration allows a calculation of TLC (V ₂ )

    
    
    
    
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      <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='V2=V1C1−C2/C2′>V2=V1(C1−C2)/C2V2=V1C1−C2/C2
      V 2 = V 1 C 1 − C 2 / C 2
      

    
    

  
  
  
  
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  The major limitation to the helium dilution technique is that only ventilated lung is measured such that patients with air trapping and bullous lung disease will have their lung volumes underestimated

  
  
  
  
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    This can erroneously lead to pseudorestriction being misinterpreted as true mixed obstructive restrictive disease

  
  
  
  
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  Body plethysmography enables measurement of RV or functional residual capacity (FRC), from which TLC is calculated by adding the VC or inspiratory capacity (maximum inhalation from a normal exhale during tidal breathing), respectively

  
  
  
  
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    Because body plethysmography assesses the total volume inside the thorax (ventilated and unventilated areas alike), it more accurately measures TLC in patients with poorly ventilated areas of the lung (eg, those with air trapping and bullous disease)

    
    
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    Body plethysmography technique:

    
    
    
    
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      The subject is seated in a sealed chamber (in which pressure is measured closely) and then instructed to exhale normally to FRC or RV

      
      
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      Next the subject is instructed to make repetitive inspiratory efforts against a sealed tube (effectively panting without moving any air)

      
      
      
      
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        As the diaphragm contracts, pressure decreases inside the thorax and the volume of air in the FRC and/or RV increases

      
      
      
      
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      Pressure in the box increases proportionately, allowing FRC or RV to be calculated

      
      
      
      
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        FRC can then be added to the inspiratory capacity (maximum inhale maneuver) to give TLC, where TLC = FRC + IC

        
        
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        RV can be added to the VC to give TLC, where TLC = RV + VC

      
      
      
      
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      Although measuring RV directly is more intuitive, it is difficult for older individuals to exhale maximally before “panting” against a closed circuit, occasionally causing syncope