While spirometry has been used to evaluate lung function for more than 200 years, the use of flow volume loops for evaluating the forced vital capacity was only first introduced by Hyatt, Schilder and Fry in 1958.1,2,3 During a forced exhalation, as the pressure in the lung increases, the pleural pressure forces pushing air out of the alveoli are also applied to the airways, narrowing them and exaggerating pathologies that reduce airflow. Once alveolar pressure reaches around 20 cmH2O, increasing effort will not affect flow (Figure 1) making the flows measured the mouth effort-independent above that pressure.
Hyatt demonstrated that the factors that determine maximum expiratory flow were also extremely dependent on lung volume and airway caliber. This has given us the most common display of lung function testing results of a flow volume curve showing decreasing expiratory flows as lung volume decreases during a forced exhalation and reflecting the patency of the airways. An additional influence during exhalation is the continual reduction in cross sectional area from the terminal airways to the trachea, thereby increasing turbulent airflow during exhalation and resistance.
Inspiratory flow in comparison, continues to increase during inspiration until a patient reaches the most negative alveolar pressure. The rapid movement of the diaphragm and chest- wall create a large negative alveolar pressure. As air enters the alveoli, the alveolar pressure becomes less negative so that maximum negative alveolar pressure is not at Total Lung Capacity. Airflow is also influenced by the rapidly increasing cross sectional area from the trachea to the terminal airways, generating more laminar flow during inhalation and lower resistance. The negative intrathoracic pressures are also applied to the airways, which increases their diameter, reducing resistance to airflow. Peak negative alveolar pressure typically occurs in the middle of inspiration from the residual volume position, which is also close to within the tidal breathing volume range (Figure 2).
Inspiratory flow therefore is rarely a cause for concern in patients with COPD as the airways are dilated during inspiration with lower resistance than during expiratory flow and it’s primarily expiratory flow that limits ventilation. However, the belief that inspiratory flow is inconsequential in obstructive disease, except for the detection of upper airway disease, is misleading. The evaluation of inspiratory flow is only inconsequential when patients have a normal Functional Residual Capacity (FRC) and can begin inspiration from a normal resting lung volume.
The maximum flow volume loop is exactly what it states; it is the outer loop of flow at maximum effort at any lung volume. When the FRC is increased, the range of peak inspiratory flow becomes reduced. Figure 3 shows multiple forced vital capacity measurements in a subject with only very mild airway disease beginning the forced inspiratory maneuver at various lung volumes. As can be seen in the figure, as lung volume increases, the peak inspiratory flow can decrease by as much as 50% from the flow potential at a normal FRC, while tracking along the maximal curve from end exhalation.
The treatment of COPD patients with inhaled drugs has seen a significant shift to dry powder inhalers (DPIs) with some reporting use in 68% of patients.12 The use of DPIs has been partially driven by the poor coordination of patients using metered dose inhalers (MDIs). Patients report that the use of a DPI is much easier than using an MDI. Table 1 identifies many of the COPD drugs available in DPI preparations and the flow required to deagglomerate and aerosolize the powder within the DPI device for delivery by inhalation.
It is clear from this table that COPD patients must generate adequate peak inspiratory flow to inhale these products. Laube has demonstrated that it is not just the peak inspiratory flow but the acceleration to peak flow that is also very important, and that the minimum flow acceleration for using blister or multidose DPIs is 0.7 L/s2.4 With an acute progression of COPD during an exacerbation, there is further narrowing of the airways, leading to gas trapping and an increasing FRC (reduction in Inspiratory Capacity). The impact of breathing at a higher lung volume therefore results in a significant reduction in peak inspiratory flows and flow acceleration. This places patients who need their drugs more than ever, but lack the ability to aerosolize the drug within their delivery device to inhale them, in a precarious situation.
Furthermore, at a higher lung volume, not only is the peak inspiratory flow lower, but the inspired volume to carry the drug to the periphery is also smaller. It has been reported that when patients use a capsule DPI, they should inhale at least 500 mL after reaching the required inspiratory flow.5 It is therefore not surprising that when COPD patients get into trouble, the slide to hospitalization or rehospitalization can be very rapid.
Sharma, et al, studied the peak inspiratory flow rates of COPD patients upon discharge for COPD-related hospitalization from seven US hospitals.6 Nearly one-third of the patients had PIFRs less than 60 LPM, meaning that on discharge, these patients might not benefit from the drugs they were prescribed for treatment of their COPD. The mean PIFR for all subjects was only 71 LPM.
When we look at this data, the high rehospitalization rate for people with COPD is not surprising. If patients don’t do well on a drug in DPI formulation, it may be that the drug isn’t working, or it could be just that the patient couldn’t aerosolize the powder and it wasn’t delivered.
Understandably, it has been demonstrated that findings of decreasing inspiratory capacity (IC) is one of the most sensitive indicator of treatment failure and exacerbation in COPD.7,8,9,10,11 If Inspiratory Capacity isn’t frequently monitored in COPD patients, the very least is that peak inspiratory flow is monitored. And consider that these are free-flow peak inspiratory flow measurements and not affected by the resistance of the DPI devices that would lower the peak inspiratory flow even further. This is another important reason why COPD patients should not be monitored with spirometers that don’t measure inspiratory flow and why we fail patients with COPD when we do. Therefore, spirometers that measure expiratory flow only should not be used to monitor patients with COPD.
- Hyatt RE, Schilder DP, and Fry DL. Relationship between maximum expiratory flow and degree of lung inflation. J Appl Physiol. 1958; 13:331-336.
- Fry DL, and Hyatt RE. Pulmonary mechanics. Amer J Med. 1960; 29:672-689.
- Jordanglou J, Pride NB. Factors determining maximum inspiratory flow and maximum expiratory flow of the lung. Thorax 1968; 23:33-37
- Laube BL, Janssens HM, de Jongh FH, Devadason SG, Dhand R, Diot P, Everard ML, Horvath I, Navalesi P, Voshaar T, Chrystyn H. What the pulmonary specialist should know about the new inhalation therapies, Eur.Respir. J. 2011; Kamin WE, Genz T, Roeder S, Scheuch G, Cloes R, Juenemann R, Trammer T. The inhalation manager: a new computer-based device to assess inhalation technique and drug delivery to the patient, J. Aerosol Med. 2003; 16:21-29.
- Sharma G, Mahler DA, Mayorga VM, Deering KL, Harshaw Q, Ganapathy V. Prevalence of Low Peak Inspiratory Flow Rate at Discharge in Patients Hospitalized for COPD Exacerbation. Journal of the COPD Foundation 2017; 4:217-224.
- Yetkin O, Gunen H. Inspiratory capacity and forced expiratory volume in the first second in exacerbation of chronic obstructive pulmonary disease. Clin Respir J. 2008; 2(1):36-40.
- Tantucci C, Donati P, Nicosia F, Bertella E, Redolfi S, DeVecchi M, Corda L, Grassi V, Zulli R. Inspiratory capacity predicts mortality in patients with chronic obstructive pulmonary disease. Respir Med. 2008; 102(4):613-9.
- Cushen B, McCormack N, Hennigan K, Sulaiman I, Costello RW, Deering B. A pilot study to monitor changes in spirometry and lung volume, following an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), as part of a supported discharge program. Respir Med. 2016; 119:55-62.
- Casanova C, Cote C, de Torres JP, Aguirre-Jaime A, Marin JM, Pinto-Plata V, and Celli BR. Inspiratory-to-Total Lung Capacity Ratio Predicts Mortality in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2005; 171:591–597.
- French A, Balf D, Mirocha JM, Falk JA, Mosenifar Z The inspiratory capacity/total lung capacity ratio as a predictor of survival in an emphysematous phenotype of chronic obstructive pulmonary disease. International Journal of COPD 2015; 10:1305–1312.
- Ramadan WH, Sarkis AT Patterns of use of dry powder inhalers versus pressurized metered-dose inhalers devices in adult patients with chronic obstructive pulmonary disease or asthma: An observational comparative study. Chron Respir Dis. 2017 Aug; 14(3): 309–320.