Pulmonary Function

Medical Pharmacology Chapter 48: Assessment of Pulmonary Function in Normal and Pathological States: An Introduction

¹²Spirometry: Definition--Spirometry measures the mechanical function of the lung, chest wall, and respiratory muscles. The method of analysis is based on an assessment of the total volume of air exhaled from a full lung, i.e. total lung capacity (TLC) to an empty lung (residual volume). For reliable assessment, this volume which represents the forced vital capacity (FVC) should be reproducible to within about 0.2 L. The process involves the patient inhaling as much as possible followed by rapid and forceful exhalation for as long as possible. The spirometry has been assigned a CPT code (94010) with a special code to cover cases in which spirometry is performed both before and after the use of bronchodilator (94060).
¹²To a first approximation a reduction in any amount is air exhaled forcefully within the first seconds of FEV, a.k.a. FEV₁ may indicate an elemental reduction in the maximum inflation capacity of the lung (TLC). The most common cause of FEV₁ reduction is airway obstruction and the use of inhalational bronchodilators determines the reversibility of airway obstruction. As noted earlier, determination this reversibility is important in development of a preanesthetic plan for patients with obstructive disease because the prophylactic use of bronchodilators may obviate interoperative pulmonary adverse events.
¹²The indication for use of spirometry includes many different endpoints in addition to preanesthetic assessment.
- Evaluation of dyspnea, determination of the presence of pulmonary disease as well as assessing the efficacy of drugs that might treat such disease, quantifying the extent of ventilatory impairment as well as monitoring for the presence or evolution of occupationally-related lung disease in addition to evaluation of operative risk all represent reasons to perform spirometric testing.
¹²In some patients there many relative contraindications for spirometry.
- Some examples include:
  1. Unstable angina
  2. Recent myocardial infarction
  3. Abdominal or thoracic aneurysm
  4. Cerebral aneurysms
  5. Recent eye surgery in which increased intraocular pressure which occurs during forced expiration would be problematic
  6. Patients with relatively recent abdominal or thoracic surgery
  7. Patients with a history of syncope associated with forced exhalation.
¹²Particularly for the perioperative or preoperative assessment, the efficacy of bronchodilators ( use of bronchodialator attenuate the likelihood of interoperative bronchoconstriction) is often determined.
- To establish a baseline in those patients who routinely take bronchodilators, the medication may be withheld with the recognition that withholding medication may in fact itself worsened bronchospasm.
- Nevertheless in order to establish baseline lung function and determine the maximal theoretical effect of bronchodilator medication might be withheld.
¹²The extent to which interoperative planning will be based on spirometry is interdependent on the validity of the spirometric test. Accordingly the quality of the tests are important and unreliable test results must be considered accordingly. Guidelines from the American Thoracic Society defines an acceptable spirometric test in the following manner:
- (1) minimal hesitation associated with the start of the forced expiratory component, specifically extrapolated volume (EV) should be < 5% of the FVC or 0.15L, whichever is larger
- (2) cough does not occur during the first seconds of forced exhalation
- (3) at least 1 of 3 criteria which define a valid end-of-test has been met:
  - (a) Smooth curvilinear rise of the line-time tracing to a plateau that lasts at least one second
  - (b) If a test fails to show a expiratory plateau but a forced expiratory time (FET) of 15 seconds obtains or
  - (c) If the patient should not to or could not continue forced exhalation for medical reasons.
¹²As suggested above, the two largest values for FVC and the two largest values for FEV₁ should vary by no more than 0.2L.
- Analysis of spirometric test problems indicate that start-of-test difficulties which effect FEV ₁assessment tend to be rare, maybe about 2%, but end-of-test difficulties which ultimately affect FVC quality are much more common, about 60%-80%.
- The quality of FVC is insured therefore if there is a 12 to 15 second expiratory time even if the expiratory plateau is not evident.
- Checking the beginning of the volume-time tracing for possible "hesitant" start is important since such hesitation can give an incorrect, underestimation of FEV₁.
- ¹²The most important 3 values for assessment of abnormal pulmonary function would be: (1) FVC, (2) FEV₁, and (3) FEV₁/FVC.

**Flow-Volume Characteristics of Acceptable and Unacceptable Spirometry**

"Instantaneous start of exhalation Rapid rise in flow to peak flow Shap peak occuring early in exhalation Smooth continuous fall in flow without interruption Gradual fall in low flow to RV Smooth continuous inhalation to TLC Reproducible shape	Slow start Slow rise in flow Broad, late peak Erratic Flow (cough) Abrupt return to 0 flow Incomplete inhalation Non-reproducible"

¹²Fixed upper airway obstruction
- Some causes:
  - Postintubation stenosis
  - Goiter
  - Endotracheal neoplasms
  - Bronchial stenosis

¹²Variable intrathoracic obstruction
- Possible causes:
  - ¹³Tracheomalacia
    - "A congenital weakness and floppiness of the walls of the trachea (main airway).
    - Tracheomalacia occurs when the cartilage in the trachea fails to develop or mature in a timely manner, resulting in the wall of the trachea being floppy rather than relatively rigid. Children with tracheomalacia have noisy breathing (high-pitched sounds when breathing, called stridor, and rattling noisy breaths) that becomes even worse if they develop upper respiratory infections."
  - ¹⁴Polychondritis
    - "Relapsing polychondritis is a disease characterized by autoimmune-like episodic or progressive inflammation of cartilage and other connective tissue, such as the nose, ears, throat, joints, kidneys, and heart.
    - As relapsing polychondritis advances, it causes more dangerous symptoms such as deterioration of the cartilage that holds the windpipe open. Progressive disease can destroy the integrity of the airway and compromise breathing. Destruction of the rib cartilage can collapse the chest, again hindering breathing. Joints everywhere are involved in episodes of arthritis, with pain and swelling. Other tissues besides cartilage are also involved, leading to a variety of problems with the skin and other tissues. Occasionally, the aorta or heart valves are damaged."
  - Tumors of the lower trachea or main bronchus

¹²Variable extrathoracic obstruction
- Possible causes:
  - Unilateral/bilateral vocal cord paralysis
  - Vocal cord constriction
  - Airway burns
  - Reduced pharyngeal cross-sectional area

¹⁵Relapsing polychondritis: A Case Study

Introduction:
- Relapsing polychondritis (RP) involves recurrent cartilaginous and connective tissue inflammation.
  - This disorder is rare in the underlying mechanism unknown.
  - Some patients with RP exhibit inspiratory abnormalities and high mortality morbidity accompany this involvement.
  - More commonly, RP manifests as auricular chondritis, nasal chondritis and polyarthritis.
  - Female patients are more likely to exhibit airway complication secondary to RP.
  - Patients with relapsing polychondritis may have operations fairly frequently for nasal reconstruction, bronchoscopy, valvular surgery, tracheobronchial stenting and tracheostomy.
  - The case report which follows provides a context for discussion of anesthetic management in patients with RP.
This patient was a female Asian of middle-age with extensive tracheobronchial involvement who underwent tracheostomy subsequent to tracheal collapse. The procedure was performed under general anesthesia.
The patient was a 48-year-old Asian woman who presented with dyspnea and exhibited productive cough for the previous eight months.
- The initial diagnosis was bronchial asthma. Helix inflammation of both ear pinnae and polyarthralgia with small and large joint involvement were also noted in the history and physical.
- Initially, bronchoscopic and chest x-ray evaluations were performed and found normal.
- The pulmonary function test predicted value (FVC) was 2.46 L. in the actual test result was 2.41 L.. The FEV₁ was 1.63 L. (Predicted value was 2.1 L.).
- The peak expiratory flow rate was 4.88 L. relative to a predicted value of 5.62 L.
- These analyses suggested mild flow obstruction that was unresponsive to bronchodilator treatment. Nasal root elevation and stridor (progressive) had been noticed by family.

**¹⁶Polychondritis-Induced Ear Redness**

**¹⁶Saddle Nose Deformity**

Upon admission, physical examination revealed voice hoarseness, saddle nose deformity and bilateral ear perichondritis. Inspiratory and expiratory stridor (resting) was observed.
- Laboratory findings were generally normal as were and electrocardiographic and neck & chest x-rays.
- Epiglottis inflammation and glottis inflammation as well as limited cord movement was revealed by bronchoscopy.
- At this point, during bronchoscopy, the patient became cyanotic with severe stridor in the decision was made to secure airway by tracheostomy under general anesthesia.
Preoperative assessment:
- Blood pressure was 154/92 mm Hg, heart rate = 102 bpm, respiratory rate = 16/min, pO₂ = 97% on room air. Preanesthetic medication included 0.6 mg atropine with 8% Xylocaine.
- Awake orotrachial intubation was implemented using direct laryngoscopy.
- As a result of a swollen epiglottis with a significantly narrowed glottic opening because of erythema and edema, only a 6 mm (internal diameter) cuffed can be used.
- Following endotracheal intubation, 5 mg/kg thiopental, 100 micrograms fentanyl and 0.4 mg/kg atracurium was administered by IV. Ventilation was controlled to allow a tidal volume of 500 ml with a respiratory rate of 10/min.. The peak inspiratory pressure was 28 cm H₂0.
- A 6.5 mm tracheostomy tube was placed in the patient sent to the recovery room. Initially, the vital signs exhibited stability (blood pressure = 130/90 mm Hg; heartrate = 100/min.; respiratory rate = 15/min.,pO₂ =99% with T-piece circuit at FiO₂ of 50%).
- Following tracheal suctioning, the patient reported respiratory difficulty.
  - O₂ saturation remained acceptable; however, blood pressure increased to 160/100 mm Hg with an attendant increased heartrate to 120/min. and an increase in respiratory rate to 25/min..
  - Bronchoscopy indicated diffuse inflammation and swelling of the entire trachea with extension to the right main bronchus.
  - Furthermore, collapse of the trachea and bronchi were visualized during inspiration and expiration. Suction applied through the bronchoscope also induced tracheal collapse.
  - Application of continuous positive airway pressure (CPAP) at 8 cm H₂0 was implemented to prevent airway collapse.
    - CPAP application reduced patient breathlessness.
    - Further treatment was implemented in the ICU. High dose corticosteroid and nonsteroidal anti-inflammatory drugs were given to suppress the inflammatory component (tracheobronchial tree).
    - Antibiotics were prescribed following identification Streptococcus viridans in the respiratory tract.
    - The recommendation was the placement endobronchial stents; however, this procedure was delayed due to the presence of to respiratory tract infection.
Discussion:
- Relapsing polychondritis (RP) is a rare disease but offers certain specific challenges to anesthesia practice because of the disease process alters the structural characteristics of cartilage which in turn present intubation challenges and challenges associated with maintenance of the patent airway.
- Although RP appears to be an inflammatory, autoimmune disease, laboratory tests to confirm the presence of RP are unavailable.
- The inflammatory component is managed with corticosteroid treatment which at least for severe cases does not stop the progressive process.
  - Relapsing polychondritis, although not noted in the case study, may also present cardiovascular challenges since cardiac involvement may include aortic and mitral valve regurgitation, pericarditis, paroxysmal atrial tachycardia, aneurysms, myocarditis, and systemic vasculitis.
- Ventilatory impairment, as a manifestation of RP, occurs in about 50% of RP patients, mainly female patients, and respiratory difficulties in the setting has a high associated morbidity and mortality.
Airway involvement can be diffuse or more localized and the involvement, especially relevant for intubation and airway maintenance, may be extrathoracic or intrathoracic (bronchi and trachea).
The airway involvement is indicated by tenderness over the anterior trachea and thyroid cartilage, sore throat, and nonproductive cough.
More severe disease include additional manifestation such as voice hoarseness, dyspnea, and stridor.
Airway obstruction in RP results from:
1. Airway narrowing (acute stage) resulting from inflammatory reactions, i.e. swelling
2. Subsequent development of scar tissue and
3. "Dynamic airway collapse" because those cartilage destruction at laryngeal, tracheal and bronchial sites. And regions exhibiting scarring and inflammation, abnormal mucociliary function predisposes to infection.
Airway assessment would include CT scans [head & neck] as well as radiography. Airway caliber changes may be identified and these changes are permanent, secondary to scarring.
- However, airway caliber dynamic changes which occur during breathing would not be revealed by radiographic techniques.
- Bronchoscopy allows direct evaluation of these dynamic changes and specifies locations and characteristics of structural abnormalities.
- Unexpected airway collapse intraoperatively can have catastrophic consequences such as death.
Anesthetic management: as noted earlier, these patients may undergo "routine" surgeries in support of tracheostomy, nasal reconstruction, bronchoscopy, valvular surgery, or tracheobronchial stenting.
- Due to loss of cartilaginous structural support, airway management becomes the central, crucial issue.
  - Accordingly, preoperative assessment concerning the extent of structural weakness is important to anesthetic plan development.
  - Cartilaginous destruction can make intubation challenging because of a small glottis. Smaller endotracheal tube sizes may be a benefit.
  - Tracheal intubation itself may be associated with sudden death secondary to tracheal collapse; however, this eventuality might be prevented by continues positive pressure mask ventilation.
  - In the case above, awake laryngoscopic intubation was used, technique allowing reasonable visualization during intubation. Following endotracheal intubation, positive pressure ventilation prevents airway collapse.
    - Fiber-optic bronchoscopy in support of intubation may be an alternative.
    - Also, general anesthesia might be avoided and instead use local or regional approaches.
    - Preoperative management might include corticosteroid use to decrease inflammation.
  - Intraoperative bronchoscopy may be useful to more completely assessed tracheobronchial involvement. The trachea might also be treated with local anesthetic through tracheostomy; such agents may reduce tracheobronchial irritability during emergence.
  - For patients with primarily (only) epiglottic or subglottic disease, tracheostomy would be indicated. Here the point is that for more generalized disease tracheostomy alone would not be expected to be effective since tracheal collapse below the tracheostomy point could be anticipated.
  - Avoidance of airway collapse in these cases then require positive pressure ventilation. With diffuse tracheobronchial relapsing polychondritis, continues positive airway pressure (CPAP) may be an effective intervention.
  - In patients with tracheomalacia, CPAP provides a "splint" which presents airway collapse.
  - Effective airway stenting might require a CPAP of about 10 cm H₂O. CPAP opposes elevated pleural pressures, maintaining therefore airway integrity.
Tracheobronchial tree mechanical stenting offers treatment alternatives (silicone stents, self-expanding stainless steel stents). Stent placement, which probably should be done early in the RP disease process, is performed under general anesthesia.

¹²Obstructive defects:
- FEV₁ reduction disproportionate compared to the FVC is a key to diagnosing obstructive lung dysfunction.
  - This characteristic would be associated with a number of lung diseases including:
    - Asthma
    - Acute/chronic bronchitis
    - Bronchiectasis
    - Emphysema
    - Cystic fibrosis
    - Pneumonia
    - Emphysema
    - -1-antitrypsin deficiency
    - Bronchiolitis.
  - For any given expiratory volume, expiratory flow be reduced. The reduction in airflow in the situation can be secondary to a number of factors including airway inflammation, increased intraluminal secretions, bronchial spasm, and/or decreased airway parenchymal support due to reduced lung elastic recoil.
- Assessment of reversibility is important in terms of developing an anesthetic planning; therefore, spirometry-determined airway obstruction raises the question of whether or not inhaled bronchodilators might be useful.
  - The American Thoracic Society has developed a minimal response that would be demonstrated in order to affirmatively decide that bronchodilator treatment is useful.
  - This minimum response corresponds to at least a 12% and 0.2 L increase in either the FVC or FEV₁ as documented by spirometry performed between 15-20 minutes following inhalation of a normal therapeutic bronchodilator dosage. In this protocol is reasonable in predicting the likelihood of bronchodilator-mediated clinical benefits; however, negative result does not mean that no clinically beneficial response might be obtained. Positive responses to bronchodilators appears to be well correlated with positive responses to steroid treatment.
¹²Restrictive defects
- Restrictive lung disease is characterized by a reduction in FVC with a normal or elevated FEV₁/FVC ratio.
¹²Spirometric quantification:
- FVC, FEV₁, and FEV₁/FVC ratios will usually be above the lower limits of normal; however, the question is how are these lower limits of normal estimated. The general approach is to define the lower limit of normal as a result that a mean predicted value -1.64 times the standard error of the estimate from the population study on which the reference is based. The reference would take into account patient gender, age and height. Should the lower limit of normal value be unavailable than the FVC and FEV₁ should be greater than or equal to 80% of predicted and the FEV₁/FVC ratio should be no more than about 8-9% below the predicted ratio. Of these two approaches, the American Thoracic Society, has recommended the use of the lower limit of normal measure rather than the 80% of predicted for setting the line below which abnormality would be concluded from the test results.
- Reduced FVC on spirometry without a reduced FEV₁/FVC ratio indicates restrictive ventilatory dysfunction. Shortened exhalation during spirometry can result in a reduced FVC. Shortened exhalation can be due to a number of factors including cardiomegaly, ascites, pregnancy, obesity, pleural effusion, kyphoscoliosis, pulmonary fibrosis, pleural tumors, neuromuscular disease, diaphragmatic weakness or paralysis, space-occupying (mass) lesions, congestive heart failure, lung resection, inadequate expiration due to pain, severe obstructive lung disease, and inadequate inspiration.
- Reductions in FVC and/or FEV₁ Classification.
  - "Mild: 70%-79% of predicted
  - Moderate: 55%-69% of predicted
  - Severe: 45%-54% of predicted
  - Very Severe: < 45% of predicted"
¹²Obese Patients:
- Special assessments include: sitting vs. supine vital capacity measurements.
  - Diaphragmatic strength assessments can be made by vital capacity measurements in patients who are either sitting or in the supine position. First measurements are made in the upright (sitting position) and then measurements made in the supine position
  - Diaphragm weakness (or paralysis) would be reflected by reduction in the vital capacity of less than 90% of the upright vital capacity.
  - Increased vital capacity reduction in the supine position may not mean diaphragmatic dysfunction if the patient is obese. In that case, resistance to obesity to diaphragm descent may explain the reduction.
¹²Interoperative and postoperative risk assessment
- FEV₁ is an important measurement for operative risk assessment associated with pulmonary impairment. The general rule is that when FEV₁ is greater than 2L or greater than about 50% of normal (predicted), significant complications are unlikely.
  - However, the surgical site is an important consideration in risk assessment. For example, chest surgery has the highest risk. Furthermore, the patient-related considerations can translate to higher operative risk due to pulmonary complications.
- Increased operative risk for pulmonary related complications is associated also with pre-existing patient conditions. Some of these conditions include: cardiovascular disease, pulmonary hypertension, exertional dyspnea, pre-existing pulmonary dysfunction, a history of heavy smoking, respiratory infection, cough, advanced age (> 70 years), poor nutrition, obesity, general debilitation, as well as the expectation of a prolonged surgical procedure.
- Lung surgery: assessment for this type of surgery requires an estimation of postoperative FEV₁ based on preoperative FEV₁. Scintigraphy (perfusion scans) may be helpful in certain ambiguous cases to more quantitatively ascertain contributions from remaining pulmonary parenchyma. Relative perfusion percentage (Q) of remaining parenchyma is thought proportional to its ventilation contribution and may be helpful in estimating postoperative pulmonary function using the following relationship:
  - postoperative FEV₁ = preoperative FEV₁ x Q% of remaining lung parenchyma. An example calculations also presented in reference 12 as follows:
    - In this example the preoperative FEV₁ is 1.6 L and lung to be resected indicates 40% perfusion. Therefore postoperative FEV₁ would be estimated by 1.6 x 0.6 or 0.96 L (i.e. 1 L). Chronic respiratory failure could be associated with an estimated postoperative FEV₁ < 0.8 L. so the 0.8 L might be used as a cut-off for acceptable operative risk. For patients with preoperative FEV₁ < 2 L or 50% of predicted, arterial blood gas values and cardiopulmonary exercise evaluation may be helpful in further assessing operative risk. The equation above for assessing operative risk in lung resection procedures has been itself validated in clinical trial (17⁾.
      - In that study patients were considered relatively safe for pneumonectomy if they exhibited a negative history for cardiovascular problems and a normal ECG and also demonstrated in FEV₁ and a pulmonary diffusing capacity for carbon monoxide (DLCO) > 80% predicted. If FEV₁ or CLVO was found less than 80% of predicted, patients would be subjected to cardiopulmonary exercise testing as part of a more complete preoperative assessment.

⁷PAS-stain Pulmonary Alveolar Proteinosis

"Granular, pink, PAS+ alveolar exudate fills alveoli.
Denser pink clumps, acicular clefts, and a few disintegrating macrophages are present in the exudate.
Electron microscopy shows myelin figures.
Lavage fluid appears milky.
Alveolar walls are only slightly thickened."

¹¹ OVD: Flow (top) and Spirometric Data (right) Characteristics