Authors: Robert Brinton Fujiki, Susan L. Thibeault
Categories: Article, Paradoxical vocal fold motion, vocal cord dysfunction, non-specific cough, habit cough, tic cough, pulmonary function tests
Source: American journal of otolaryngology
Authors: Robert Brinton Fujiki, Susan L. Thibeault
To determine the diagnostic utility of spirometry in distinguishing children with Induced Laryngeal Obstruction (ILO) or chronic non-specific cough (a.k.a. tic cough) from those with mild or moderate to severe asthma.
Retrospective cross sectional design. Children diagnosed with ILO (N=70), chronic non-specific cough (N=70), mild asthma (N=60), or moderate to severe asthma (N=60) were identified from the electronic medical record of a large children’s hospital. Spirometry was completed before ILO, non-specific cough, or asthma diagnoses were made by pediatric laryngologists or pulmonologists. Spirometry was performed following American Thoracic Society guidelines and was interpreted by a pediatric pulmonologist. Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), FEV1/FVC Ratio (FEV1/FVC), Forced Mid-Expiratory Flow 25–75% (FEF25–75%), pulmonologist interpretation of flow volume loops, and overall exam findings were extracted from the medical record.
Ninety seven percent of children with ILO or chronic non-specific cough presented with spirometry values within normative range. Patients with ILO, non-specific cough, and mild asthma presented with FVC, FEV1, FEV1/FVC, and FEF25–75% values in statistically similar range. Children with moderate to severe asthma presented with significantly reduced FVC (p<.001), FEV1 (p<.001), FEV1/FVC (p<.001), and FEF25–75% (p<.001) values when compared with patients in the other groups. Flow volume loops were predominantly normal for children with ILO and non-specific cough.
Findings indicate that ILO and chronic non-specific cough can neither be diagnosed nor differentiated from mild asthma using spirometry alone. Spirometry should therefore be used judiciously with this population, bearing in mind the limitations of the procedure. Future research should determine the most effective and efficient ways of delineating ILO and non-specific cough from other respiratory conditions in children.
Dyspnea and cough symptoms commonly bring children to primary care physicians for diagnosis and treatment.^1–3^ Identifying the underlying etiology of these manifestations, however, can be challenging.^4,5^ Both dyspnea and cough may portend dangerous respiratory pathologies that demand urgent medical treatment.^6^ Similar symptoms, however, may also result from conditions treated by laryngologists and speech-language pathologists (SLP) such as laryngeal obstruction (ILO) and non-specific cough (a.k.a. tic cough).^7,8^ It is important that these conditions be accurately and efficiently identified^9,10^ as ILO and non-specific cough can be frightening and debilitating,^11,12^ impeding quality of life^12,13^ and burdening families financially.^14,15^ Fortunately, once identified, ILO and non-specific cough respond well to behavioral therapies provided by SLPs.^8,16–19^
ILO is characterized by inappropriate laryngeal adduction upon inhalation which results in dyspnea.^20^ The condition has had numerous names (i.e., paradoxical vocal fold movement, vocal cord dysfunction)^18,21–24^ and is characterized by inhalation difficultly, chest or throat tightness, dizziness, and other manifestations.^5,25,26^ Symptoms may be triggered by a variety of factors including irritants,^27^ stress,^28^ and exercise (when induced by exercise, the term Exercise Induced Laryngeal Obstruction [EILO] is used).^29–31^ ILO symptoms are often transient in nature and resolve with trigger removal.^32^ The condition is relatively common, occurring in as many as 8% of adolescents in the general population.^33–35^
Chronic non-specific cough consists of a non-specific cough lasting >4 weeks (in the absence of a somatic symptom disorder).^36^ Non-specific or tic cough, previously referred to as habit cough,^37^ resembles a tic clinically.^38^ Non-specific cough tends to be suppressible, variable, suggestable, and generally absent when the child is asleep.^36,39^ The condition can resolve on its own, but it may persist for years if left untreated.^19^ Prevalence is unknown, however, non-specific cough makes up 12.3% of pediatric cough cases.^4^
Diagnosing ILO and non-specific cough can be challenging since both conditions share common symptoms with asthma and other respiratory conditions.^8,40^ Asthma, which affects as many as 14% of children and adolescents worldwide,^41^ is characterized by chronic lower respiratory inflammation^42^ and may present as dyspnea, wheezing, or even cough.^43^ In cough-variant asthma, cough is the primary symptom.^44^ Since asthma is widely recognized among general practitioners and the general population,^45^ children with ILO and non-specific cough often receive asthma treatments/testing such as inhalers or pulmonary function testing/spirometry.^46^ This is unfortunate because inhalers are of questionable value in treating non-specific cough or ILO.^46^ In addition, although spirometry may effectively identify asthma,^47^ it is not clear if it effectively differentiates ILO or non-specific cough from other common respiratory conditions such as asthma.
Spirometry measures inhalation and exhalation, as a function of time.^48^ Measures of lung capacity and expiratory volumes over time can indicate when a patient presents with obstructive lung disease.^49^ This is useful for identifying conditions such asthma, interstitial lung disease, or chronic obstructive pulmonary disease.^47,50,51^ Additionally, research in adults suggests that patients with ILO may present differently on spirometry measures when compared with controls.^52–54^ It has been reported that spirometry measures of forced vital capacity (FVC) and expiratory volume over 1 second (FEV1) are reduced in patients with ILO.^53,55^ Other research has described truncated inspiratory flow volumes in this population.^56^ On the other hand, multiple studies suggest that adult patients with ILO present with normal spirometry values,^57–59^ even following exercise.^60^ When differences have been observed, sensitivity has been low across most studies.^53^ Additional investigation focusing on pediatric populations is needed to determine the usefulness of spirometry for children and adolescents with ILO.
Considering that non-specific chronic cough etiology differs between adult and pediatric populations,^9,61^ examination of spirometry data in adults with chronic refractory cough may have little applicability to children. Even so, it has been suggested that normal spirometry findings in children with cough can support the diagnosis of non-specific cough.^36^ Data regarding spirometry findings in children with non-specific cough are very limited, however, and the utility of spirometry in differentiating specific pathologies is questionable.
Clarifying the diagnostic utility of spirometry in children is important as evidence suggests that children with ILO often undergo this procedure and that it can be expensive for patients.^62^ The most common justification for the use of spirometry in children with ILO and non-specific cough is to rule out other respiratory conditions^36,53^ – usually asthma.^63^ As such, the current study considered two whether children with ILO and non-specific cough scored within normative range on spirometry and whether spirometry distinguished children with these diagnoses from children with mild and moderate to severe asthma. It was hypothesized that children with ILO or non-specific cough would present with normal spirometry values, while children with mild asthma would present with mildly reduced values. It was also hypothesized that patients presenting with moderate to severe asthma would present with significantly reduced spirometry values compared to all other diagnostic groups.
A retrospective cross sectional design was employed. All study procedures were approved by the relevant institutional review board. Children diagnosed with ILO, non-specific cough, or mild, moderate, or severe asthma were identified from the electronic medical record using ICD-10 and CPT codes between the years of 2015 and 2022. All children had undergone spirometry testing prior to formal diagnoses of the aforementioned conditions. Spirometry was performed in either the outpatient pediatric pulmonary or allergy labs of a large pediatric hospital. Results were interpreted by pediatric pulmonologists. Children presenting with confounding respiratory conditions were excluded. Children were also excluded if they could not complete spirometry testing to the criteria of the American Thoracic (ATS) and European Respiratory Societies (ERS).^64^
ILO and non-specific cough were diagnosed by a pediatric laryngologist following laryngoscopy. For ILO, laryngoscopy followed exercise if symptoms were exercise induced. Continuous laryngoscopy is the most accurate diagnostic test for EILO^65–67^ but is not commonly available throughout the United States.^68^ As such, laryngoscopy following exercise is frequently employed in research and clinic contexts.^16^ Asthma was diagnosed by pediatric pulmonologists using patient history and evidence of reversible airway obstruction on bronchoprovocation/methacholine challenge testing. Asthma severity was determined by pediatric pulmonologists and was rated as either mild, moderate, or severe.
Basic demographic information was extracted for all children. Data included age, sex/gender, and BMI. Additionally, for children with ILO or non-specific cough, disease symptoms were extracted. Spirometry was completed in accordance with ATS/ERS guidelines.^64^ All measures were calculated on the best of three trials and were reported as percentages of normal predicted values. Included measures were defined as follows.
Forced Vital Capacity (FVC) represents the full amount of air that an individual can forcibly exhale in one complete breath.^48^ In pediatric populations, observed values ≥80% of predicted value were considered within normal range.^48^ Forced Expiratory Volume in 1 Second (FEV1) represents the volume of air that an individual can forcibly expel over 1 second.^48^ Observed values ≥80% of predicted value were considered within normal range.^48^ FEV1/FVC Ratio (FEV1/FVC) is frequently used to diagnose obstructive lung disease and measures the proportion of an individual’s vital capacity that can be expelled over the first second of FVC.^48^ Observed values ≥80% of predicted value were considered within normal range.^48^ Forced Mid-Expiratory Flow 25–75% (FEF25–75%) represents forced expiratory flow at 25% to 75% of FVC.^48^ Observed values ≥80% of predicted value were considered within normal range.^48^
Pulmonologist interpretation of spirometry testing was extracted as well as the interpretation of inspiratory and expiratory flow volume loops. Finally, if patients were diagnosed with evidence of obstructive pulmonary disease, this was rated as either mild, moderate, or severe by the pediatric pulmonologist.
Descriptive statistics were calculated for all outcome measures. Additionally, mixed level modeling was used to compare spirometry values across all diagnoses. Percent of predicted measures were analyzed to control for patient demographics. Fixed factors in the model included diagnosis (ILO, non-specific cough, mild asthma, moderate to severe asthma), sex/gender (male, female), and a diagnosis*sex/gender interaction. Age and BMI were included in the model as covariates. Participant was included as a random factor in order to account for individual variation. Tukey’s LSD tests were used for post hoc comparisons. Alpha was set at .05 for determining statistical significance.
Medical record review initially identified 311 candidates for the current study. Fifty-one children were excluded because spirometry data were incomplete or respiratory diagnosis could not be confirmed. Thus, 260 children were included in analysis. Of these, 70 presented with ILO, 70 with non-specific cough, 60 with mild asthma, and 60 with moderate or severe asthma. Distribution of patient ages and sex/gender across diagnostic groups is presented in Table 1. Mean ages were 15.05 years for the ILO group, 10.2 for the non-specific cough group, 14.1 for mild asthma, and 13.1 for those with moderate to severe asthma.
Means for all measures are presented in Table 1. For FVC, a significant effect of diagnosis was observed (F(3, 252)=6.74, p<.001). This occurred because FVC values for the moderate to severe asthma group (M=90.3) were significantly reduced when compared with the ILO (M=102.3, p<.001), non-specific cough (M=104.5, p<.001), or mild asthma groups (M=101.3, p=.002). Additionally, a significant effect of sex/gender was observed (F(1, 252)=4.81, p=.029). This indicated that values were greater for males than for females (males=102.3, SD=1.8; females=96.9, SD=1.5; p=.02).
For FEV1, a significant effect of diagnosis was observed (F(3, 252)=10.2, p<.001). This occurred because FEV1 values for the moderate to severe asthma group (M=82.3) were significantly reduced when compared with the ILO (M=100.7, p<.001), non-specific cough (M=100.6, p<.001), or mild asthma groups (M=96.6, p<.001). Additionally, a significant effect of sex/gender was observed (F(1, 252)=6.65, p=.01). This reflected greater values for males than for females (males=98.5, SD=2.0; females=91.6, SD=1.7; p=.02).
For FEV1/FVC, a significant effect of diagnosis was observed (F(3, 250)=8.29, p<.001). This occurred because FEV1/FVC values for the moderate to severe asthma group (M=87.6) were significantly reduced when compared with the ILO (M=95.7, p<.001), non-specific cough (M=96.3, p<.001), or mild asthma groups (M=95.5, p<.001).
For FEF25–75%, a significant effect of diagnosis was observed (F(3, 250)=24.8, p<.001). This occurred because FEF25–75% values for the moderate to severe asthma group (M=61.7) were significantly reduced when compared with the ILO (M=99.5, p<.001), non-specific cough (M=92.3, p<.001), or mild asthma groups (M=92.8, p<.001).
Over 97% of children with ILO scored within normal range on FVC, FEV1, FEV1/FVC, and FEF25–75%. Above 97% of patients with non-specific cough also scored within normal range, except on FEF25–75%, where 87% of patients scored within normal range. For patients with mild asthma, >91% of patients scored within normative range across all parameters, except on FEF25–75%. On FEF25–75%, 81.5% of patients scored within normal range. For those with moderate to severe asthma, 75.7% of patients scored within normal range on FVC, 48.3% on FEV1, 68.3% on FEV1/FVC, and 25% on FEF25–75%.
Regarding overall spirometry findings, 3.3% (N=2) of patients with mild asthma and 7.1% (N=5) of patients with ILO presented with a truncated expiratory loop. No patients in the moderate to severe asthma group, or in the non-specific cough group presented with truncated expiratory loops. Truncated inspiratory volume loops were observed in 5% (N=4) of those with ILO, and 6% (N=4) of those with moderate to severe asthma. No children in the other groups presented with truncated inspiratory loops. Additionally, all patients in the moderate to severe asthma group presented with evidence of obstructive airway disease. This was determined to be moderate in 50% (N=30) cases and severe in 50% of cases (N=30). For patients with mild asthma, 18.3% (N=11) of patients presented with evidence of mild obstructive pulmonary disease and the remainder presented with normal spirometry. For those with ILO, 5.7% (N=4) presented with evidence of mild obstructive pulmonary disease, and 1.4% (N=1) presented with evidence of moderate obstruction. For patients with non-specific cough, 12.9% (N=9) presented with potential evidence of mild obstruction.
ILO and non-specific cough can be frightening, frustrating, limiting, and detrimental to quality of life for children.^11,12^ Despite being relatively common, these conditions are difficult to diagnose as their symptoms overlap with more familiar conditions.^36,69^ As such, children may undergo significant testing prior to diagnosis.^62^ One of the most common diagnostic tests applied in this population is spirometry,^8,23^ which measures inhalation and exhalation as a function of time.^70^ The usual justification for spirometry is to rule out asthma - the most common respiratory condition that may be confused with ILO and non-specific cough.^71–73^ The current study considered two questions - whether children with ILO and non-specific cough scored within normative range on spirometry and whether spirometry distinguished children with these diagnoses from children with varying severities of asthma. It was hypothesized that children with ILO or non-specific cough would present with normal spirometry values, while children with mild asthma would present with reduced values. This hypothesis was partially confirmed as children with ILO, non-specific cough, and mild asthma all scored within statistically similar range. Additionally, 97% of children with ILO or non-specific cough, and 91% of children with mild asthma, scored within normal range. It was also hypothesized that patients presenting with moderate to severe asthma would present with values significantly reduced compared to all other diagnostic groups. This was confirmed, as FVC, FEV1, FEV1/FVC, and FEF25–75% were all significantly reduced for children with moderate to severe asthma when compared to those with ILO, non-specific cough, or mild asthma.
In the current population, spirometry did not significantly differentiate children with ILO or non-specific cough from those with mild asthma – and values for all three groups were predominantly in normative range. This finding supports past work in adults indicating that patients with ILO often have normal spirometry testing.^58^ This finding differs, however, from other investigations suggesting that adults with ILO present with truncated inspiratory loops on spirometry.^53^ The vast majority of children with ILO and non-specific cough presented with normal flow volume loops in the current study. When flow volume loops were truncated, it was equally likely to be the inspiratory or expiratory loops which were affected. Current findings also differ from past study in adults suggesting that FEV1 is often reduced in patients with ILO.^5^ This difference in findings could reflect the fact that this measure decreases with age in adult populations.^74^ It could also reflect the fact that the proportion of athletes in pediatric ILO patients is high,^34,75^ and athletes often present with elevated spirometry values.^76^ Increased baseline spirometry values in this population, may mean that values are more likely to remain within normative range – even if a decline should occur. Thus, athletes with ILO in the current study may have continued to present with normal spirometry values. Regardless, none of the examined measures, including FEV1, reliably distinguished children with ILO or non-specific cough from children with mild asthma or children without any airway disease. Thus, clinicians should be cognizant of the limitations of spirometry in this population.
The current study suggests that if the primary goal is to rule out mild concurrent asthma, spirometry is of limited use. This finding is important considering that spirometry can be expensive^77^ and is not always covered by patients’ insurance. Clinically, we have observed that care providers who are unfamiliar with ILO or non-specific cough may prescribe multiple bouts of spirometry prior to diagnosis with the primary goal of determining whether asthma is the etiology of dyspnea or cough. Additionally, it should be noted that truncated inspiratory/expiratory loops are not a reliable indicator of ILO in pediatric populations. Increased understanding of ILO and non-specific cough might prevent unnecessary testing.
Spirometry was effective in separating children with moderate to severe asthma from those with ILO or non-specific cough. This finding supports past work indicating that children with more significant asthma symptoms do not score within normative range on spirometry testing.^78^ It should be noted, however, that past study has also indicated that spirometry values are not always correlated with clinician or patient perception of asthma symptom severity.^79^ Thus, spirometry may identify when more severe asthma symptoms contribute to dyspnea symptoms, but still does not rule out the possibility of ILO or non-specific cough, as bronchoconstriction may induce laryngeal obstruction.^5^
One challenge in differentiating ILO and non-specific cough from asthma is that diagnosing asthma can be complex in and of itself.^80^ Past work indicates that asthma diagnosis is prone to difficulties with both sensitivity and specificity.^80,81^ Additionally, as indicated previously, asthma and ILO or non-specific cough may coexist.^72,82^ In these cases, spirometry – and even bronchodilator response or methacholine challenge testing--may be necessary. Still, diagnosis may be challenging as 43% of patients with asthma may test negative for the condition on bronchodilator response testing.^83^ Even methacholine challenge testing does not always have strong negative predictive value.^84^ Thus, these tests should be employed judiciously, taking into account thorough patient medical history to determine when the procedure is indicated.
It should be noted that normal spirometry values do not rule out the possibility of either anatomical or physiological airway disease. Individuals with chronic respiratory symptoms may present with normal values on spirometry yet may continue to experience poor respiratory outcomes or symptoms.^85^ Thus, it cannot be assumed that children with normal spirometry scores require no further treatment. This is particularly pertinent for children with ILO or non-specific cough who can present with debilitating symptoms that are not reflected by this procedure.
Prospective study may help to determine what testing or respiratory measures can best clarify the relationship between conditions such as ILO, non-specific cough, and asthma. Although it was beyond the scope of the current study to examine the diagnostic ability of bronchodilator response or methacholine challenge testing in patients with ILO or non-specific cough, the children in the ILO and non-specific cough groups overwhelmingly presented with normal baseline scores, rendering bronchodilation less useful.^86^ Additionally, the current study examined ILO, non-specific cough, and varying severities of asthma, but it did not consider the ability of spirometry to delineate ILO and non-specific cough from other respiratory conditions, including other types of chronic cough.
Children with ILO or chronic non-specific cough largely presented with spirometry values within normative range. FVC, FEV1, FEV1/FVC, and FEF25–75% values were statistically indiscernible from each other or from patients diagnosed with mild asthma. Patients with moderate to severe asthma presented with significantly lower values on these measures when compared to patients in the other groups. These findings suggest that ILO and chronic non-specific cough cannot be differentiated from mild asthma or diagnosed from spirometry alone. Spirometry should therefore be used judiciously with this population bearing in mind the limitations and advantageous of the procedure. Future research should investigate measures best suited to identify and distinguish ILO, non-specific cough, and asthma in children.