Pulmonary Function Testing

##Technique

• spirometer should be calibrated daily with a 3L syringe.
• testing should be done on physiologic normals

4 Phases

• Maximum inspiration
• BLAST expiration
• complete expiration (EOFE acceptability criteria: plateau of expiration to <25cc/s, 15s elapsed, or 3 repeatable/consistent measures)
• inspiration @ maximum flow (the FIVC, which should confirm that the loop started at max inspiration).

Repeatability = less than 150 cc between efforts for FEV1 and FVC. Repat for up to 8 times to get 3 that are repeatable. Acceptability = each effort. Needs to meet EOFE criteria and no cough in 1st second, no leak, etc.

Shunt Study

Alternative method to quantify impairment in oxygenation of the blood.

Idea = use hyperoxia to wash out all nitrogen from the alveoli. Then, only oxygen and CO2 are left.

Assumption 1: Assume pO2 in the blood is over 150 - thus, you are way out on the O2Hb dissociation curve. Thus, the addition of further oxygen is unlikely to result in signficantly higher Content of O2 (CaO2 - because this is only the small dissolved content)

Assumption 2: the consumption of blood in the periphery results in a 5ml/dl decrease in O2 content in the mixed venous blood. This is empirically in the right ballpark for folks who are supine and not metabolically stressed. (theoretically, you could measure it).

With those assumptions....

• Qt (total blood flow) = Qs (shunt flow) + Qc (capillary flow = all non-shunt flow)
• CaO2 * Qt = (CvO2 * Qs) + (CcO2 * [Qt-Qs]). CaO2 = arterial o2 content in blood, v = mixed venous (since blood through the shunt is never oxygenated), c = end-capillary blood.

If fully saturated (PaO2 150+), SaO2 and ScO2 are roughly equal -> Berggren equation: [side note, I'm not sure this can really hold - as if it were true.. it'd be possible for people to maintain adequate O2 without any Hb?]

• Qs/Qt = P(A-a)O2 * 0.0031 / [P(A-a)O2 * 0.031] + 5 (assumed).

##non specific pattern

Low fvc but normal tlc pleth

Seem in early airways disease - because the patchy disease will cause some air units to not contribute to either fev1 or fvc- or small airways eg bronchiolits w air trapping on CT

Or

Early mechanical problems such as nm weakness

Obstruction

Algorithm for ambiguous cases

##Restrictive pattern FVC and FEV1 can be suggestive of restriction, but requires TLC to confirm. (Conversely, if FVC is normal - 98% predictive value for absence of restriction).

• Simple restriction: FEV1, FVC, and TLC all decreased roughly in proportion. More likely to have ILD
• Complex restriction: FVC is disproportionally decreased in comparison to TLC (== relatively increased RV, RV/TLC ratio) - suggestive of a superimposed process on top of ILD. More likely to have NM dz, diaphragm paralysis, bronchiectasis, mosaic attenuation on CT, or pulm HTN.

DOI: http://dx.doi.org/10.1016/j.chest.2017.07.009

Changes in Obesity

Citation: doi:10.1152/japplphysiol.00694.2009

Restriction not due to mechanical load on chest wall - it is due to decreased compliance of the respiratory system (?increased atelectasis, increased intrathoracic fat - as well as pressure on diaphragm from visceral adipose) - this is supported by:

1. maximum inspiratory and expiratory pressures being similar in overweight and normal weight subjects (e.g. no hypertrophy of those muscles)
2. Paralyzed subjects have parallel but rightwardly shifted compliance curves (e.g. it is a threshold load, not stiffening) Citation: Behazin N, Jones SB, Cohen RI, Loring SH. Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity.J Appl Physiol 108: 212–218, 2010.

Decreased ERV and FRC - usually associated with increased closing volume suggestive of small airway closure and air trapping. Decreases in FRC are reliable and exponential, starting with only modestly overweight subjects. Restriction (meaning decrease in TLC) - present in only ~20% of super obese, 40% of super super obese.

Note: restriction on PFTs is not synonymous with obesity hypoventilation syndrome - both impaired mechanics and reduced respiratory drive likely contribute (as well as confounding presence of OSA)

https://journal.chestnet.org/article/S0012-3692(20)31415-X/pdf

Provocation challenges

To diagnose airway hyperresponsiveness in asthma. Idea: 20% fall in FEV1 after administering the provocation = positive test.

Note: at a high enough dose, many if not all subjects will have a response. Thus, PC20 dose is important and false positives are possible (reference standard is an issue)

False positives known in: allergic and nonallergic rhinitis (4-5%), obesity. PPV in random subjects as low as 50% (with cutoff 8mg/mL methacholine)

False negatives: in seasonal allergies, if they have been asymptomatic in days (e.g. no exposure to allergic antigen), will be negative

There are direct and indirect methods:

Direct (high sensitivity, low specificity): methacholine (ACh ag), histamine (not used anymore). Start with low dose, then increase dosage until a response is observed = PC20

Indirect (low sensitivity, high specificity - as stimuli is more physiologic): exercise, eucapnic voluntary hyperpnea, hypertonic saline, adenosine monophosphate, mannitol

Eucapnic voluntary hyperpnea

Breath from bag of 21% O2, 5% CO2 at near MVV (5% inspired CO2 keeps PaCO2 near normal)

Previously gold standard for exercise induced bronchospasm for IOC (no longer required for albuterol). Inter-test reproducibility is poor, thus probably does not warrant reference standard status.

CHEST 2010; 138(2)(Suppl):18S–24S

Aging

Diaphragm Weakness

Source: NEJM 2012 - DOI 10.1056/NEJMra1007236

Partial loss of ability to generate pressure = weakness; loss of ability = paralysis.

Unilateral paralysis: usually asymptomatic, but may have DOE or exercise limitation. Less commonly supine dyspnea.

Bilateral paralysis or significant weakness: significant dyspnea or recurrent respiratory failure, sleep hypoventilation. Provoked supine, with water above the waste. Abdominal paradox on exam (inward movement of abdomen during inspiration caused by intercostals / SCM doing the work, doesn't occur in unilateral and doesn't occur until MIF < 30).

Course: injury to phrenic nerve alone can resolve (1-3 years - commonly cold water related to cardiac surgery), SCI C3-5 or higher will not (C3: 40% need vent, C4-5 15%). Progressive (e.g. ALS) will not improve. Post-polio mean onset of diaphragm weakness = 35 yrs

Diagnosis

• CXR: Se 90%, Sp 44% for unilateral paralysis. Bilateral process is very hard to differentiate from "poor inspiratory effort".

• Fluoroscopy "Sniff Test": not helpful for bilateral, paradoxical movement in unilateral paralysis

• PFTs: baseline - unilateral may have mild restriction; bilateral may have marked. Supine: unilateral paralysis or bilateral weakness will lead to 10-30 FVC drop. Bilateral: 30-50% FVC drop. If no drop, clinically significant weakness is unlikely. FRC and RV are usually normal.

• US: can measure thickening of the diaphragm (corresponds to crosslinking of myosin fibers) - should increase during inspiration.

Comorbid with sleep disordered breathing by several mechanisms:

• suppression of accessory inspiratory muscules during REM sleep
• pharyngeal and laryngeal muscle weakness leading to upper airway collapse

Plethysmography

Ref: Cree 2011 AJRCCM

Lung volumes:

• spirometry (VA sb) - measures accessible (within 10s breath hold) lung

• plethysmography TLC - measures FRC (total amount of compressible gas in the thorax. Beware if large hiatal hernia) and can infer TLC based on spirometric measurement of inspiratory capacity (FRC+IC = TLC)

VAsb / TLCpleth < 0.8 = incomplete gas mixing.

Boyle-Marriotte's Law: P * V = constant. Thus: P1 * V1 = (P1+ change in P) * (V1 * change in V)

Shift Volume

Change in volume (delay) that reflects resistance of air movement. Relies on the fact that change doesn't happen instantaneously.

Keep in mind, at FRC, pressure = 0 aka atm (because resting). PL

Change in PL can be measured by mouthpiece

Change in VL = shift volume (the amount that moves in past the mouthpiece. Corresponds to the negative of V_pleth)

Thus, you can solve for

Change in PL / PL = change in VL (shift volume) / VL (aka FRC - most technically, compressible gas In the thorax)

Change in Press to change in vol plot will steepen with smaller FRC, flatter with larger FRC.

Airways resistance

Can estimate driving pressure using change in pressure in the plethysmograph (because you know the change in volume into the lung by measuring at the mouth piece, which is equal but negative of change in plethysmograph volume), then you measure the pressure in the plethysmograph to estimate pressure in airway. This is done against an open shutter.

Note: this is different than spirometry estimated resistance because it's done at resting breathing as opposed to maximal effort.

sRaw: volume and resistance-dependent work of breathing to generate 1.0 L/sec

Raw: change in lung pressure needed to achieve a flow rate of 1.0 L/sec

sRaw = Raw * FRC

Implication - for a given airway resistance, more work if the lung volume is bigger. Additionally, for a given lung volume, more resistance requires more work for the same flow.

Inspiratory = above line, expiratory = below line. **right?

1. Normal - not much volume change needed to generate flow

2. Large airway resistance - more volume change needed for flow

3. Widening = ???

5. Upper airway obstruction - much more work required as you inspire (=flatter)

Gaw and sGaw = conductance, just reciprocal of Raw

Minor patterns with signficance

PRISM - isolate low FEV1, but normal FVC and normal TLC

Nonspecific - low FVC, normal TLC - can be early obstruction, restriction, (or neither? 
Complex Restriction - low FVC, Low TLC but not as low as expected. Mayo

Size of RV predicts: ILD (low) vs NM blockade (middle) vs Airtrapping and restriction (highest)

Neuromuscular testing

MIP positive MEP negative

Q: are muscles weak? weak enough to be responsible for Low VC or SOB or retained secretions?

MIP < 30% predicted -> resp failure in NM dz MEP < 60 cmh2o predicts ineffective cough

Pressures are dependent on lung volume (?and lung compliance, airway disease). Highest MIP = RV (FRC is about 15% lower) Highest MEP = TLC

Need flange mouthpiece. Tech dependent (awkward)

Thus, order only if high pretest.

Low MIP, normal MEP => pattern consistent with diaphragm weakness Seated/Supine - useful in that case: 10-30% decrease = unilateral weakness, 30% = bilateral weakness. Occurs due to superior displacement decreases muscular advantage (will lead to abdominal paradox when supine)

Seated/supine,

VC and MVV - VC: sensitive for mod/severe resp weakness - str < 50% before VC < LLN. Low VC and no other explanation (ie. not obese, no pleural process) -> NM testing

MVV: very effort dependent and influenced by other factors - reduced in proportion to VC and thus adds little if you have VC (MVV = 40* VC), MIP, and MEP. Don't order, generally.