Original Studies
Wheezing in Children With Pertussis Associated With Delayed Pertussis Diagnosis Zackary W. Taylor, MD,*† Bradley Ackerson, MD,† David E. Bronstein, MD,† Kaeryn Lewis, MD,† Evan Steinberg, MD,† Margaret M. Stone, MD,† Roopa Viraraghavan, MD,† Victor K. Wong, MD,† and Mark B. Salzman, MD† Background: The classic clinical features of paroxysmal pertussis are often absent in older children and adults and after vaccination. The California pertussis epidemic of 2010 occurred in a highly vaccinated population. Methods: All pediatric patients (0–18 years) with positive pertussis polymerase chain reaction from July to December 2010 were identified retrospectively from the Kaiser SCAL database. Information extracted by chart review included age at diagnosis, vaccine history, race, cough duration, number of clinic visits before diagnosis, presence of paroxysms, post-tussive emesis or wheezing, treatment for asthma during the course of illness and exposure to confirmed or suspected pertussis cases. Results: Overall 501 pediatric patients (mean age = 8.4 years) with positive pertussis nasopharyngeal polymerase chain reaction were identified. Complete DTaP series and Tdap vaccine had been received by 93% and 38% of eligible patients, respectively. Paroxysms, post-tussive emesis and wheezing on physical examination were present in 34%, 30% and 8% of patients, respectively. Each was associated with a longer duration of symptoms at diagnosis. Wheezing was associated with a delay in diagnosis (60% requiring >1 clinic visit for diagnosis vs. 29% in the overall population, P < 0.0001). Documented exposures were associated with a more timely pertussis diagnosis (after 9.4 days vs. 14.5 days; P < 0.0001). Conclusions: Wheezing is present on examination of some patients with pertussis in a highly vaccinated pediatric population and appears to delay the diagnosis of pertussis. The presence of wheezing should not be used to exclude this diagnosis in children with chronic cough or other reasons to suspect pertussis. Key Words: pertussis, wheezing, atypical, epidemic (Pediatr Infect Dis J 2014;33:351–354)
A
lthough classic pertussis is a well-described and distinctive clinical entity, atypical forms of pertussis are increasingly recognized in the era of pertussis vaccination.1,2 The World Health Organization (2000) and Centers for Disease Control (1997) have established a clinical case definition3 that depicts the paroxysmal phase of disease, defining a case as a coughing illness of ≥14 days with either a distinctive inspiratory “whoop,” paroxysmal cough or post-tussive emesis. However, this definition appears inadequate to identify many cases of mild disease, as vaccination has been shown to limit the duration and clinical severity of disease, to the point where vaccine trials have been criticized for not including milder, atypical cases and thus inflating the apparent efficacy of the vaccine.2,4 Some studies have shown pertussis infections to be asymp-
From the *Kaiser Permanente Medical Center, Fontana; and †Southern California Permanente Medical Group, Pasadena, CA. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Zackary W. Taylor, MD, Kaiser Permanente Medical Center, 9985 Sierra Ave, MOB-2, Fontana, CA 92335. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3304-0351 DOI: 10.1097/INF.0000000000000176
tomatic or atypical in a majority of cases.5,6 Adjunct testing through serology and polymerase chain reaction (PCR) have helped identify such cases, and the true incidence of pertussis is being established only now.3 A rising incidence of pertussis in older children and adults, leading to an increase in infant infections and several deaths in the more severely affected young infant age group, is now well-documented.7–10 Waning immunity after acellular pertussis vaccination is probably partly to blame for this increase,2,8,11 but underrecognition of atypical disease in adults and older children may also play a part in maintaining a reservoir of infection in those age groups.1 Pertussis epidemics tend to occur in late summer and early fall, as typified by the California epidemic to be described here, and recur in cyclical fashion. Although there was a relative lull in pertussis in 2011, the year following the California epidemic, there have since been several epidemics in 2012, including 1 in Washington state.9,12 The incidence of pertussis in 2012 was higher than the preceding year in 49 of 50 states and in Washington, DC,12 and recurrent pertussis epidemics are likely to continue for several years to come. During this time, it will be important to minimize the spread of disease during such epidemics through prompt recognition and treatment of suspected cases. The pertussis epidemic in California was declared in June 2010 and most cases were recognized in Southern California in the latter half of the year. With the large numbers of pertussis cases appearing in our clinics during that time, we undertook an assessment of vaccine efficacy and in the process of recording clinical data for that larger study (pending publication), we recognized that some patients with pertussis were initially misdiagnosed as having an asthma exacerbation, often with wheezing noted. Previous experience has shown an increase in pertussis diagnosis among asthmatic patients,13 although it is unclear whether asthma affects the timeliness of pertussis diagnosis. A retrospective cohort study of the pertussis-positive patients was thereby undertaken to assess the extent to which clinical and demographic characteristics observed in pertussis cases were associated with the timing of pertussis diagnosis.
MATERIALS AND METHODS In this retrospective cohort study, the pediatric population (≤18 years) of Kaiser Permanente Southern California (KPSC) with documented positive nasopharyngeal PCR for pertussis were reviewed from the period of highest pertussis activity (July to December 2010). Data extracted from patients’ charts included: gender, age at the time of pertussis diagnosis, duration of cough before diagnosis, vaccination history, number of medical visits for the illness before diagnosis (including evaluation by a physician in a clinic or emergency room), month of diagnosis, presence of wheezing on examination, report of paroxysms or post-tussive emesis and treatment for asthma exacerbation (with an inhaled beta-agonist or oral steroid) during the illness course. Patients, who had received a vaccine 1 visit for their ongoing symptoms by the time of pertussis diagnosis. Significantly more visits before diagnosis were observed for those patients with paroxysms, post-tussive emesis or wheezing (Table 1). Treatment for asthma exacerbation during the coughing illness was common ( n = 122 patients, 22%) before diagnosis of pertussis, and a minority of these patients (31%) had wheezing on examination. Nearly all patients with wheezing (n = 38; 95%) were initially treated as a presumed asthma exacerbation, although only 43% (n = 23) of these patients had a history of asthma. When the wheezing was further qualified by the examining physician, the mild end of the spectrum was described. The most common qualifier was “occasional wheezing,” with “trace” and “rare,” also used in several charts; descriptors of moderate wheezing severity, “diffuse” and “modest,” were each only used once and severe wheezing or restricted air movement were not described. Among those patients treated for asthma, with or without wheezing on examination, diagnosis of pertussis was made significantly later in the disease course [14.9 (SD: 10.5) days; P = 0.01], and in those with wheezing a similar trend was noted (Table 2). In adolescents, duration of cough before pertussis diagnosis was longer than for other age groups [ages 11–18 years: 14.5 (SD: 9.7) days vs. ages 0–10 years: 11.7 (SD: 9.5) days; P = 0.002] but conversely, slightly fewer medically attended visits were required to make a pertussis diagnosis in an adolescent (only 23% of adolescents required a second visit vs. 33% of those 1 clinic visit for diagnosis; versus Tdap-recipients: 14.8 days (P = 0.6); 32% required >1 visit (P = 0.1). The clinician’s reasoning for pertussis testing beyond clinical symptoms was not consistently documented, but exposure to contacts with confirmed or suspected pertussis was often noted. This documentation was assessed in 433 patients, of whom 20% were found to have such an exposure. Of those cases, 58% (24% confirmed and 34% suspected by the interviewing clinician) were in the household, the rest being at school (17%) or other/unspecified contacts (24%). Documentation of such confirmed or suspected exposures was associated with a much shorter duration of symptoms before diagnosis [9.4 (SD: 8.9) days vs. 14.5 (SD: 9.6) days; P < 0.0001; Fig. 1, Table 2) and a more prompt diagnosis upon presentation to medical care (only 18% requiring >1 clinic visit for diagnosis; P = 0.006). When the presence of wheezing, age, interval since last pertussis vaccine and positive exposure history were included in a Cox proportional hazard model for the length of symptoms before diagnosis, only a positive exposure history remained a significant predictor of more rapid pertussis diagnosis [hazard ratio (HR) 1.5, P=0.001 vs. wheezing HR 0.88, P = 0.5; age HR = 0.98, P = 0.3; vaccine interval HR = 0.99, P = 0.7]. If multivariate regression is performed with the same independent variables as predictors of the number of clinic visits before © 2013 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 33, Number 4, April 2014
Wheezing and Pertussis
TABLE 1. Demographics and Diagnostic Precision, Relating to Presenting Features of Pertussis*
Age (years) Gender (% female) Received Tdap (%)‡ Cough duration before diagnosis (days) >1 visit before Dx (%) overall >1 visit (%) among infants 1 visit (%) among 0–10 years of age† >1 visit (%) among 11–18 years of age†
Wheezing (N = 40)†
Paroxysms (N = 168) †
Post-tussive emesis (N = 150)†
All pertussis patients (N = 501)†
8.6 SD= 4.1 (P = 0.8) 44% (P = 0.4) 58% (P = 0.1) 15.2 SD= 9.9 (P = 0.1) 60% (P < 0.0001) 100% (P = 0.006) 70% (P < 0.0001) 38% (P = 0.1)
8.5 SD= 4.9 (P = 0.5) 51% (P = 0.6) 45% (P = 0.2) 14.9 SD = 10.4 (P = 0.0006) 41% (P = 0.0001) 47% (P = 0.01) 48% (P < 0.0001) 28% (P = 0.3)
8.0 SD= 4.8 (P = 0.3) 53% (P = 0.4) 43% (P = 0.4) 14.6 SD = 9.4 (P = 0.007) 43% (P = 0.0001) 53% (P = 0.008) 49% (P < 0.0001) 29% (P = 0.2)
8.4 SD = 4.9 50% 38% 12.8 SD = 9.7 29% 38% 33% 23%
*Clinical variables are not mutually exclusive and a single patient may show several presenting features (ie, being included in several columns). P-values were assessed with Student t test (for age and cough duration), χ2 (for gender and receipt of Tdap) and Wilcoxon-Mann-Whitney test (for # visits), by comparing the group with the variable of interest against the rest of the study population (or the rest of the population in the specific age group). The mean value is listed for age, cough duration and number of visits. The SDs are listed for normally distributed variables. Bold text indicates a significant difference or trend in the variable of interest. †Among age subgroups, sample sizes were smaller: among patients aged
Wheezing in Children With Pertussis Associated With Delayed Pertussis Diagnosis Zackary W. Taylor, MD,*† Bradley Ackerson, MD,† David E. Bronstein, MD,† Kaeryn Lewis, MD,† Evan Steinberg, MD,† Margaret M. Stone, MD,† Roopa Viraraghavan, MD,† Victor K. Wong, MD,† and Mark B. Salzman, MD† Background: The classic clinical features of paroxysmal pertussis are often absent in older children and adults and after vaccination. The California pertussis epidemic of 2010 occurred in a highly vaccinated population. Methods: All pediatric patients (0–18 years) with positive pertussis polymerase chain reaction from July to December 2010 were identified retrospectively from the Kaiser SCAL database. Information extracted by chart review included age at diagnosis, vaccine history, race, cough duration, number of clinic visits before diagnosis, presence of paroxysms, post-tussive emesis or wheezing, treatment for asthma during the course of illness and exposure to confirmed or suspected pertussis cases. Results: Overall 501 pediatric patients (mean age = 8.4 years) with positive pertussis nasopharyngeal polymerase chain reaction were identified. Complete DTaP series and Tdap vaccine had been received by 93% and 38% of eligible patients, respectively. Paroxysms, post-tussive emesis and wheezing on physical examination were present in 34%, 30% and 8% of patients, respectively. Each was associated with a longer duration of symptoms at diagnosis. Wheezing was associated with a delay in diagnosis (60% requiring >1 clinic visit for diagnosis vs. 29% in the overall population, P < 0.0001). Documented exposures were associated with a more timely pertussis diagnosis (after 9.4 days vs. 14.5 days; P < 0.0001). Conclusions: Wheezing is present on examination of some patients with pertussis in a highly vaccinated pediatric population and appears to delay the diagnosis of pertussis. The presence of wheezing should not be used to exclude this diagnosis in children with chronic cough or other reasons to suspect pertussis. Key Words: pertussis, wheezing, atypical, epidemic (Pediatr Infect Dis J 2014;33:351–354)
A
lthough classic pertussis is a well-described and distinctive clinical entity, atypical forms of pertussis are increasingly recognized in the era of pertussis vaccination.1,2 The World Health Organization (2000) and Centers for Disease Control (1997) have established a clinical case definition3 that depicts the paroxysmal phase of disease, defining a case as a coughing illness of ≥14 days with either a distinctive inspiratory “whoop,” paroxysmal cough or post-tussive emesis. However, this definition appears inadequate to identify many cases of mild disease, as vaccination has been shown to limit the duration and clinical severity of disease, to the point where vaccine trials have been criticized for not including milder, atypical cases and thus inflating the apparent efficacy of the vaccine.2,4 Some studies have shown pertussis infections to be asymp-
From the *Kaiser Permanente Medical Center, Fontana; and †Southern California Permanente Medical Group, Pasadena, CA. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Zackary W. Taylor, MD, Kaiser Permanente Medical Center, 9985 Sierra Ave, MOB-2, Fontana, CA 92335. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3304-0351 DOI: 10.1097/INF.0000000000000176
tomatic or atypical in a majority of cases.5,6 Adjunct testing through serology and polymerase chain reaction (PCR) have helped identify such cases, and the true incidence of pertussis is being established only now.3 A rising incidence of pertussis in older children and adults, leading to an increase in infant infections and several deaths in the more severely affected young infant age group, is now well-documented.7–10 Waning immunity after acellular pertussis vaccination is probably partly to blame for this increase,2,8,11 but underrecognition of atypical disease in adults and older children may also play a part in maintaining a reservoir of infection in those age groups.1 Pertussis epidemics tend to occur in late summer and early fall, as typified by the California epidemic to be described here, and recur in cyclical fashion. Although there was a relative lull in pertussis in 2011, the year following the California epidemic, there have since been several epidemics in 2012, including 1 in Washington state.9,12 The incidence of pertussis in 2012 was higher than the preceding year in 49 of 50 states and in Washington, DC,12 and recurrent pertussis epidemics are likely to continue for several years to come. During this time, it will be important to minimize the spread of disease during such epidemics through prompt recognition and treatment of suspected cases. The pertussis epidemic in California was declared in June 2010 and most cases were recognized in Southern California in the latter half of the year. With the large numbers of pertussis cases appearing in our clinics during that time, we undertook an assessment of vaccine efficacy and in the process of recording clinical data for that larger study (pending publication), we recognized that some patients with pertussis were initially misdiagnosed as having an asthma exacerbation, often with wheezing noted. Previous experience has shown an increase in pertussis diagnosis among asthmatic patients,13 although it is unclear whether asthma affects the timeliness of pertussis diagnosis. A retrospective cohort study of the pertussis-positive patients was thereby undertaken to assess the extent to which clinical and demographic characteristics observed in pertussis cases were associated with the timing of pertussis diagnosis.
MATERIALS AND METHODS In this retrospective cohort study, the pediatric population (≤18 years) of Kaiser Permanente Southern California (KPSC) with documented positive nasopharyngeal PCR for pertussis were reviewed from the period of highest pertussis activity (July to December 2010). Data extracted from patients’ charts included: gender, age at the time of pertussis diagnosis, duration of cough before diagnosis, vaccination history, number of medical visits for the illness before diagnosis (including evaluation by a physician in a clinic or emergency room), month of diagnosis, presence of wheezing on examination, report of paroxysms or post-tussive emesis and treatment for asthma exacerbation (with an inhaled beta-agonist or oral steroid) during the illness course. Patients, who had received a vaccine 1 visit for their ongoing symptoms by the time of pertussis diagnosis. Significantly more visits before diagnosis were observed for those patients with paroxysms, post-tussive emesis or wheezing (Table 1). Treatment for asthma exacerbation during the coughing illness was common ( n = 122 patients, 22%) before diagnosis of pertussis, and a minority of these patients (31%) had wheezing on examination. Nearly all patients with wheezing (n = 38; 95%) were initially treated as a presumed asthma exacerbation, although only 43% (n = 23) of these patients had a history of asthma. When the wheezing was further qualified by the examining physician, the mild end of the spectrum was described. The most common qualifier was “occasional wheezing,” with “trace” and “rare,” also used in several charts; descriptors of moderate wheezing severity, “diffuse” and “modest,” were each only used once and severe wheezing or restricted air movement were not described. Among those patients treated for asthma, with or without wheezing on examination, diagnosis of pertussis was made significantly later in the disease course [14.9 (SD: 10.5) days; P = 0.01], and in those with wheezing a similar trend was noted (Table 2). In adolescents, duration of cough before pertussis diagnosis was longer than for other age groups [ages 11–18 years: 14.5 (SD: 9.7) days vs. ages 0–10 years: 11.7 (SD: 9.5) days; P = 0.002] but conversely, slightly fewer medically attended visits were required to make a pertussis diagnosis in an adolescent (only 23% of adolescents required a second visit vs. 33% of those 1 clinic visit for diagnosis; versus Tdap-recipients: 14.8 days (P = 0.6); 32% required >1 visit (P = 0.1). The clinician’s reasoning for pertussis testing beyond clinical symptoms was not consistently documented, but exposure to contacts with confirmed or suspected pertussis was often noted. This documentation was assessed in 433 patients, of whom 20% were found to have such an exposure. Of those cases, 58% (24% confirmed and 34% suspected by the interviewing clinician) were in the household, the rest being at school (17%) or other/unspecified contacts (24%). Documentation of such confirmed or suspected exposures was associated with a much shorter duration of symptoms before diagnosis [9.4 (SD: 8.9) days vs. 14.5 (SD: 9.6) days; P < 0.0001; Fig. 1, Table 2) and a more prompt diagnosis upon presentation to medical care (only 18% requiring >1 clinic visit for diagnosis; P = 0.006). When the presence of wheezing, age, interval since last pertussis vaccine and positive exposure history were included in a Cox proportional hazard model for the length of symptoms before diagnosis, only a positive exposure history remained a significant predictor of more rapid pertussis diagnosis [hazard ratio (HR) 1.5, P=0.001 vs. wheezing HR 0.88, P = 0.5; age HR = 0.98, P = 0.3; vaccine interval HR = 0.99, P = 0.7]. If multivariate regression is performed with the same independent variables as predictors of the number of clinic visits before © 2013 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 33, Number 4, April 2014
Wheezing and Pertussis
TABLE 1. Demographics and Diagnostic Precision, Relating to Presenting Features of Pertussis*
Age (years) Gender (% female) Received Tdap (%)‡ Cough duration before diagnosis (days) >1 visit before Dx (%) overall >1 visit (%) among infants 1 visit (%) among 0–10 years of age† >1 visit (%) among 11–18 years of age†
Wheezing (N = 40)†
Paroxysms (N = 168) †
Post-tussive emesis (N = 150)†
All pertussis patients (N = 501)†
8.6 SD= 4.1 (P = 0.8) 44% (P = 0.4) 58% (P = 0.1) 15.2 SD= 9.9 (P = 0.1) 60% (P < 0.0001) 100% (P = 0.006) 70% (P < 0.0001) 38% (P = 0.1)
8.5 SD= 4.9 (P = 0.5) 51% (P = 0.6) 45% (P = 0.2) 14.9 SD = 10.4 (P = 0.0006) 41% (P = 0.0001) 47% (P = 0.01) 48% (P < 0.0001) 28% (P = 0.3)
8.0 SD= 4.8 (P = 0.3) 53% (P = 0.4) 43% (P = 0.4) 14.6 SD = 9.4 (P = 0.007) 43% (P = 0.0001) 53% (P = 0.008) 49% (P < 0.0001) 29% (P = 0.2)
8.4 SD = 4.9 50% 38% 12.8 SD = 9.7 29% 38% 33% 23%
*Clinical variables are not mutually exclusive and a single patient may show several presenting features (ie, being included in several columns). P-values were assessed with Student t test (for age and cough duration), χ2 (for gender and receipt of Tdap) and Wilcoxon-Mann-Whitney test (for # visits), by comparing the group with the variable of interest against the rest of the study population (or the rest of the population in the specific age group). The mean value is listed for age, cough duration and number of visits. The SDs are listed for normally distributed variables. Bold text indicates a significant difference or trend in the variable of interest. †Among age subgroups, sample sizes were smaller: among patients aged
