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Surgical treatment of acute recurrent throat infections in children
Auris Nasus Larynx 38 (2011) 356–361 www.elsevier.com/locate/anl
Surgical treatment of acute recurrent throat infections in children§ Giovanni Motta a,1, Erik Esposito b, Sergio Motta a,*, Nicola Mansi c, Vincenzo Cappello a, Bernardino Cassiano b, Gaetano Motta d a
Institute of Otorhinolaryngology, Department of Preventive Medical Sciences, Azienda Universitaria ‘‘Ateneo Federico II’’, Via S. Pansini n.5, 80100, Naples, Italy b Department of Otorhinolaryngology, Azienda Ospedaliera Santa Maria della Pieta` di Nola, Naples, Italy c Struttura Complessa di Otorinolaringoiatria, Azienda Ospedaliera di Rilievo Nazionale Santobono-Pausillipon, Naples, Italy d Department of Otorhinolaryngology, II University of Naples, Italy Received 19 January 2010; accepted 7 November 2010 Available online 15 January 2011
Abstract Objective: The purpose of this study was to define the contribute of surgery and watchful waiting in the treatment of feverish episodes and other clinical manifestations related to acute recurrent throat infections in children. Methods: An observational, retrospective and multi-centric study was carried out on 407 subjects, aged 2–11, with a minimum two-year follow-up. Chi square test and Fisher’s test were used for the statistical analysis. Results: Watchful waiting prevented, similarly to surgery, recurrences of feverish episodes, but did not favourably impact on other clinical manifestations (respiratory obstruction, otitis media, group A beta hemolyticus streptococcus positive laboratory findings) as compared to surgery ( p < 0.001). Conclusions: The higher effectiveness of surgical treatment, as compared to watchful waiting, was documented in the study patients, considering all the clinical manifestations related to acute recurrent throat infections. # 2010 Elsevier Ireland Ltd. All rights reserved. Keywords: Acute recurrent throat infections; Children; Adeno-tonsillectomy; Watchful waiting
1. Introduction Recent Randomized Controlled Trials (RCTs) aimed to establish the effectiveness of adeno-tonsillectomy (AT) and adenoidectomy (A) in the treatment of acute recurrent throat infections and otitis media in children [1–5]. On the basis of the results obtained, ‘‘Guidelines’’ have been proposed with the aim to clearly defining the indications to surgery [6–8]. The purpose of our study was to verify the outcomes of adeno-tonsillectomy in the treatment of acute recurrent throat infections in children and to compare the therapeutic contribute of surgery and watchful waiting for feverish §
No funds were received in support of this study. * Corresponding author. Tel.: +39 081 7462988; fax: +39 081 7463592. E-mail addresses: [email protected], [email protected] (S. Motta). 1 Now retired.
episodes (FE) and other clinical manifestations related to acute recurrent throat infections.
2. Materials and methods An observational, multi-centric and retrospective study was carried out in four ENT units of the city and county of Naples, in Italy (1. University of Naples ‘‘Federico II’’; 2. 2nd University of Naples; 3. Azienda Ospedaliera Santa Maria della Pieta` di Nola; 4. Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon). Inclusion criteria for the study patients were: a positive medical history of acute recurrent throat infections, characterised by FE, associated or not to other clinical manifestations (naso-pharyngeal respiratory obstruction; ASO titre elevation; rheumatoid distant disorders; otitis media with effusion and acute recurrent otitis media), patients aged between 2 and 11, and
0385-8146/$ – see front matter # 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2010.11.002
G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361 Table 1 Distribution for gender and age of the study cases. WW = watchful waiting. Sex/age
Males Females 2–3 yy. 4–5 yy. 6–7 yy. 8–9 yy. 10–11 yy.
1st investigation
in the range of normality, regardless of the test technique used, in two measurements effected at an interval of 4–6 months during the 18 months prior to the patient being included in the research. ASO titre was evaluated in two subsequent examinations at an interval of 4–6 months from each other in the follow-up period. Cases with ASO titre reentered in the limits of the range of normal values were calculated and considered as cured. Rheumatoid disorders were studied by drawing on the necessary clinical and laboratory examinations; any resolution of rheumatoid disorders was excluded or confirmed on the basis of clinical and laboratory findings. (4) Otitis media with effusion and acute recurrent otitis media. Otitis media with effusion was to be established by clinical examination and type B tympanogram obtained at least twice in the 18 months prior to the patient’s inclusion in the research. Analysis of clinical findings was conducted at the end of follow-up. As for acute recurrent otitis media (defined as 3 episodes in the last 6 months or 4 episodes in the last year), patients with 1 acute inflammatory ear episodes in the follow-up period were considered as cured. The adeno-tonsillar volume was evaluated through a clinical examination and rhinofibroscopy in all cases, but the symptomatologic aspects were privileged as compared to objective findings for the aim of the present study. The study cases were divided into three groups (Fig. 1). The group 1 comprised 183 subjects who had undergone AT, and in whom the FE were >4 in the last year. The group 2 consisted of 177 patients who underwent AT, and in whom the FE were 4. The group 3 included 47 cases in whom FE were 4 in the last year and no surgery had been performed. This last group consisted of children whose parents had refused any indication for surgical treatment; in this group appropriate medical treatment was administered (antibiotics, non-steroid anti-inflammatory drugs, corticosteroids) at the time of inflammatory clinical recurrences. The decision to proceed to AT was taken for all cases after having unsuccessfully administered medical treatment (general and local antibiotic therapy, local corticosteroid therapy, etc.) at the time of inflammatory clinical recurrences for at least twelve months. In brief, of the 407 cases studied, 360 underwent AT and 47 formed the control group. The first investigation (Fig. 1) involved groups 1 and 2 (360 subjects consisting of 221
2nd investigation
FE > 4 183
FE 4 177
Total 360
AT 177
WW 47
Total 224
109 74 19 78 60 13 13
112 65 31 94 35 10 7
221 139 50 172 95 23 20
112 65 31 94 35 10 7
22 25 6 10 12 11 8
134 90 37 104 47 21 15
a minimum two-year follow-up. Exclusion criteria were as follows: craniofacial malformations, immunodeficiency syndromes, children who underwent adenoidectomy alone, and the existence of confirmed or not yet-defined genetic disorders. Children with 1 FE or even with 2 FE in the last year, but in whom the average FE incidence in the preceding two years had been <3 per year were not included in the study. The study involved 407 subjects (243 males and 164 females), aged between 2 and 11 (Table 1), who came consecutively for their first clinical examination to the above units between (a) 1st January and 31st December 2001, to the first three centres involved in the research, (b) from the 1st January to 31st March 2001, to the fourth centre. The present research was performed in accordance of the local institutional review board guidelines, as well as the Helsinki Declaration of 1975, revised in 1983. The outcome measures were as follows: (1) FE secondary to acute recurrent throat infections. During these episodes body temperature had to be 38 8C for at least three days. The study patients were evaluated according to the number of FE in the last year, >4 episodes or 4. As for the analysis of the results, we considered the average number of FE per year for each patient in the 24 months after surgery or first clinical observation (control group). Patients with FE < 1 for year in the two years following the treatment were considered as cured. (2) Naso-pharyngeal respiratory obstruction secondary to hyperplasia of pharyngeal lymphatic tissue. Two distinct grades of respiratory obstruction were considered: slight/moderate (frequent ‘‘colds’’ with rhinorrhea; openmouth breathing during sleep) and severe grade (continuous rhinorrhea; day and night open-mouth breathing; frequent and prolonged episodes of nocturnal apnoea). Nasal breathing was evaluated 24 months after surgery or after the first observation (control group). Patients with diurnal and night time nasal breathing in the follow-up period were considered as cured. (3) ASO titre elevation and distant disorders potentially due to GABHS (group A beta hemolyticus streptococcus) infection. ASO titre was considered as a more reliable immunologic indicator of a streptococcal infection as compared to cultural tests of pharyngo-tonsillar flora, in agreement with Martin [9]. ASO titre was esteemed an indicator of a recent GABHS infection if it had increased twice or more compared to the upper limit
357
[()TD$FIG]
407 cases
FE > 4 183 cases
FE < 4 224 cases 2nd Investigation
1st Investigation
AT 183 cases (group 1)
AT 177 (group 2)
WW 47 cases (group 3)
Fig. 1. Scheme of the study, indicating the subdivision of the sample in two investigations. WW = watchful waiting; FE = feverish episodes.
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G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361
Table 2 Incidence and cure rate of clinical manifestations in the study sample in the first investigation. FE = feverish episodes; NPRO = naso-pharyngeal respiratory obstruction; EOM = otitis media with effusion; AROM = acute recurrent otitis media. NS = no significant. FE
NPRO Slight/moderate
Severe
Baseline incidence of clinical manifestations FE > 4 183/360 47.5% 33.3% 50.8% p NS <0.001 FE 4 177/360 41.8% 53.7% 49.2% Total 360 44.7% 43.3% 100% Cure rate of clinical manifestations after treatment FE > 4 155/183 95.4% 95.1% 84.7% p 0.005 NS NS FE 4 167/177 100% 93.7% 94.3% Total 322/360 97.5% 94.2% 89.4%
Abnormal ASO titre
Rheumatoid distant disorders
EOM
AROM
80.8%
67.2%
22.4%
30.6%
45.3%
<0.001 95.5%
<0.001 26.0%
<0.001 7.3%
NS 37.8%
NS 51.4%
88.0%
46.9%
15.0%
34.2%
48.3%
95.3%
67.4%
68.3%
87.5%
92.8%
NS 96.4%
NS 76.1%
0.04 100%
NS 85.1%
NS 82.4%
95.9%
69.8%
75.9%
86.2%
87.3%
Total
males and 139 females) who underwent AT but in whom FE was, respectively, >4 (group 1: 183 cases) and 4 (group 2: 177 cases). In the second investigation (Fig. 1) 224 patients were examined (134 males and 90 females) in whom 4 FE were documented in the 12 months prior to inclusion in the study and who came from groups 2, 3, respectively. More precisely, 177 cases proceeded to AT (group 2) and 47 children (group 3) made up the control group (watchful waiting). The study children were assessed every 6–12 months, for at least two years. Post-operative haemorrhagic complications were observed in 6 cases (1.6%), divided in primary (2 cases; 0.5%) and secondary (4 cases; 1.1%) haemorrhages; these haemorrhages required an adequate haemostasis in the operating room and one day of hospitalization. No complications were found in relation to the practiced medical treatments in the control group. Chi square test, with Bonferroni inequality test and Yates correction when necessary, and Fisher’s test – for
comparison of small groups – were used for the statistical analysis, assuming p < 0.05 as minimum value of statistical significance.
3. Results A complete list of the results obtained in the study patients has been reported in Tables 2 and 3. First investigation (Table 2). In the two years after intervention FE were 1 in 89.4% of cases. Children rate with FE < 1 per year in the two years following the treatment was 84.7% for FE > 4 group and 94.3% for FE 4 group ( p = 0.005). Naso-pharyngeal respiratory obstruction normalized after surgery in 95.9% of cases without any significant difference between 4 versus >4 FE cases ( p > 0.05). Abnormal ASO titre normalized in 118 out of 169 cases (69.8%) after surgery. Distant rheumatoid disorders were resolved in 75.9% of cases; this percentage resulted significantly higher
Table 3 Incidence and cure rate of clinical manifestations in the study sample in the second investigation. WW = watchful waiting; FE = feverish episodes; NPRO = naso-pharyngeal respiratory obstruction; EOM = otitis media with effusion; AROM = acute recurrent otitis media. NS = no significant. Treatment
FE 4
NPRO Slight/moderate
Baseline incidence of clinical manifestations AT 177/177 41.8% 100% WW 47/47 46.8% 100% p NS Cure rate of clinical manifestations after treatment AT 167/177 100% 94.3% WW 41/47 36.4% 87.2% p NS <0.001
Abnormal ASO titre
EOM
AROM
Severe
Total
53.7%
95.5%
25.9%
37.8%
51.4%
27.7%
74.5%
29.8%
31.9%
23.4%
<0.01
<0.001
NS
NS
<0.01
93.7%
96.4%
76.1%
85.1%
82.4%
30.8%
34.3%
28.6%
0%
9.9%
<0.001
<0.001
<0.001
<0.001
<0.001
G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361
( p = 0.04) in the group with EF 4 as compared to EF > 4 group. Resolution of inflammatory ear manifestations after AT occurred in 86.2% (otitis media with effusion: 106/123) and 87.3% (acute recurrent otitis media: 152/174) of the study patients. Second investigation (Table 3). FE were <1 per year in the two years following the treatment in 94.3% of patients operated with AT and in 87.2% of the control patients ( p > 0.05). Naso-pharyngeal respiratory obstruction normalized in a statistically higher percentage ( p < 0.001) of cases in the surgical group (96.4%) compared to the control group (34.3%). Following surgery, abnormal ASO titre normalized in a statistically higher percentage of cases (76.1%) in the surgical group ( p < 0.001) as compared to the control group (28.6%). Rheumatoid distant disorders were found in 10/177 cases (5.6%) who had to undergo AT; in all these children distant disorders completely resolved during the follow-up period. Rheumatoid disorders were not observed in the control group at the baseline. Resolution of otitis media with effusion and acute recurrent otitis media appeared to be significantly higher in the group that had undergone surgical treatment as compared to control group ( p < 0.001).
4. Discussion The aim of our investigations was primarily to evaluate the indications to AT for acute recurrent throat infections in children. In the present study we preferred to privilege the symptomatologic manifestations of adeno-tonsillar pathology (number of FE, degree of naso-pharyngeal respiratory obstruction, rheumatoid disorders, otitis media) compared with the objective findings (degree of hypertrophy of adenoids and palatine tonsils), since the number of FE could be not correlated to the size of palatine tonsils and adenoids and considering that both tonsillar and adenoideal volumes can interfere in the pathogenesis of naso-pharyngeal respiratory obstruction. The first investigation of the present study compared the findings related to the incidence of symptoms in groups with FE > 4 and 4 per year before and after surgery. The percentage rate of children in whom an improvement for the outcome measures was documented was high in both study groups, without statistically significant difference in their comparison, except for FE, for which the cure rate resulted statistically lower in group with FE > 4. In the second investigation, the obtained data showed a marked reduction in FE in the two groups of patients, albeit lower in the watchful waiting group than that observed in the surgical group, without statistically significant difference in their comparison. AT enabled high rates of success for all the clinical manifestations considered (naso-pharyngeal respiratory obstruction, ASO titre, otitis media with effusion and acute recurrent otitis media) in the study group, independently on their percentage incidence and severity at the baseline. In the control cases, on the other hand, the
359
percentage rates of cured cases were disappointing in statistically significant terms – except for FE – compared to those obtained by surgical treatment. These data demonstrate how the effectiveness of one form of treatment cannot be assessed by referring to one clinical manifestation alone: obviously, a treatment option cannot be considered efficacious when it leads to, for instance, FE being cured but does not resolve otitis media and/or naso-pharyngeal respiratory obstruction or vice versa. It must be underlined that the cure rates resulted statistically higher in the surgical group, despite the watchful waiting group showed a less serious clinical picture with regard to the baseline incidence of symptomatologic manifestations. Our results differ with those of clinical trials that aimed to identify the most effective treatments for acute recurrent throat infections in childhood [3,4,10,11]. This discrepancy could depend on the partial assessment of the clinical manifestations related to acute recurrent throat infections, as also suggested by the work of Van den Akker et al. [12], and on an underestimation of the surgical outcomes in the mentioned studies, due to different methodological factors. In the study by Paradise et al. [3], the percentage of subjects who had undergone surgery but were lost to follow-up was higher (32/35%) as compared to control subjects (12/16%). The authors reported a reduction in the number of FE in control subjects in the third year of follow-up; nonetheless, 59 study cases (over one third of the operated patients) were excluded from the research because operated on urgently. In 2002 [10], Paradise et al. resumed their research in order to establishing if tonsillectomy was appropriate in cases with less severe symptoms than in the previous investigation [3]. The study showed a statistically significant reduction in the average number of significant episodes and moderate/severe episodes, and likewise in GABHS infections, in children who underwent tonsillectomy or AT versus the control subjects for the 3 years of follow-up globally considered; furthermore, in more than 20% of the control cases surgery was effected. In relation to the high number of surgical complications (7.9%), the authors maintained that benefits for patients surgically treated were moderate as compared to risks. The lack of data concerning the assessment of respiratory nasal obstruction and post-operative ear pathology in children enrolled in the 2-way trial (AT versus control) in the study of Paradise et al. [10] was also questioned by Rosefsky [13]. Van Staaij et al. assessed the effectiveness of AT in children whose recurrent pharyngeal infections or tonsil hypertrophy gave rise to moderate clinical manifestations [4]: fewer episodes of pharyngeal infections, throat infection and inflammations of the upper respiratory tracts were documented in operated subjects as compared to controls. Nevertheless, the authors asserted that surgery only affords modest benefits compared to watchful waiting. In a subsequent meta-analytical study, Van Staaij et al. [11] analyzed the results of A and AT in patients aged under 18. The effects of interventions on sleep obstructive respiratory disorders or on upper tract respiratory obstruc-
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G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361
tion were not considered. The authors concluded that A and AT lead to a further though modest reduction in the incidence of throat infection episodes and other related manifestations compared with control subjects, substantially agreeing with Paradise [3,10] about advising surgery in cases in whom the number of pharyngeal infections exceeds seven episodes in the last year [14,15]. In our opinion, on the contrary, surgical treatment could be considered appropriate even in cases with a lower number of FE, but with evidence of respiratory obstruction and/or otitis media with effusion/ acute recurrent otitis media and/or positive laboratory findings for GABHS infections. Previous investigations also questioned the effectiveness of surgery in the treatment of inflammatory ear pathology in children [5,16]. Paradise et al. [5] carried out two trials on 461 patients drawn from a series which initially consisted of 2122: on the basis of their results, they concluded that A and AT showed a limited effectiveness: 11 cases of the control subjects (11/98 = 11%) in the first trial and 17 (17/78 = 22%) in the second underwent surgery; these subjects were presumably excluded from the calculation, like those who had been ‘‘lost’’, since they had not completed the follow-up. Oomen et al. [16] stated that surgical treatment did not give any advantage as compared to controls for otitis media: in their work, only in 111/300 cases indication for surgery was dependent on otitis media, hearing impairment or upper respiratory tracts inflammatory disorders; moreover, 50/149 cases of controls (34%) underwent surgery and were excluded from the study. In two recent Clinical Practice Guideline [17,18], the American Academy of Paediatrics stated unequivocally that reservations on the usefulness of A and AT in the treatment of otitis media should not be taken into consideration if specific indications for such operations are found. Our considerations are not intended to criticize the results of the mentioned studies; they dispute, instead, the practice of extending these to the treatment of acute recurrent throat infections in children as a whole. As such, the possibilities and limits that RCTs and retrospective investigations have in this field of clinical practice should be well known and analyzed. It seems that in this respect Schon and Stanley’s remarks [19] are particularly appropriate when they state: ‘‘. . .we can now ask to what extent should physicians rely on RCTs as opposed to clinical experience or observational studies. Unlike the comparison with basic science, we cannot simply say that they are complementary and that we need both. As discussed above, observational studies essentially are clinical experience made systematic, and RCTs are observational studies subject to further controls’’.
5. Conclusions The obtained results revealed that watchful waiting, unlike surgery, did not influence significantly the clinical manifestations related to acute recurrent throat infections in
the study patients as compared to surgery, except for feverish episodes. The higher effectiveness of surgical treatment was documented in the study patients, considering all the clinical manifestations related to acute recurrent throat infections. The data of the present study dispute the practice of extending the results of RCTs to the treatment of the acute recurrent throat infections in children as a whole, supporting the need for an integration of findings obtained through different investigative methods.
References [1] Burton MJ, Towler B, Glasziou P. Tonsillectomy versus non-surgical treatment for chronic/recurrent acute tonsillitis. Cochrane Database Syst Rev 1999;(2). doi: 10.1002/14651858.CD001802 [Art. No.: CD001802]. [2] Lim J, McKean M. Adenotonsillectomy for obstructive sleep apnoea in children. Cochrane Database Syst Rev 2001;(3). doi: 10.1002/14 651858.CD003136 [Art. No.: CD003136]. [3] Paradise JL, Bluestone CD, Bachman RZ, Colborn DK, Bernard BS, Taylor FH, et al. Efficacy of tonsillectomy for recurrent throat infection in severely affected children: results of parallel randomized and nonrandomized clinical trials. N Engl J Med 1984;310:674–83. [4] van Staaij BK, van den Akker EH, Rovers MM, Hordijk GJ, Hoes AW, Schilder AG. Effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy: open, randomised controlled trial. BMJ 2004;329:651–6. [5] Paradise JL, Bluestone CD, Colborn DK, Bernard BS, Smith CG, Rockette HE, et al. Adenoidectomy and adenotonsillectomy for recurrent acute otitis media: parallel randomized clinical trials in children not previously treated with tympanostomy tubes. JAMA 1999;282:945–53. [6] Williams A, Lee P, Kerr A. Scottish Intercollegiate Guidelines Network (SIGN) guidelines on tonsillectomy: a three cycle audit of clinical record keeping and adherence to national guidelines. J Laryngol Otol 2002;116:453–4. [7] American Academy of Otolaryngology – Head and Neck Surgery. 2000 clinical indicators compendium, vol. 19, no. 6. Alexandria, VA; 2000. p. 19 [Bulletin June 2000]. [8] Materia E, Baglio G, Bellussi L, Marchisio P, Perletti L, Pallestrini E, et al. The clinical and organisational appropriateness of tonsillectomy and adenoidectomy – an Italian perspective. Int J Pediatr Otorhinolaryngol 2005;69:497–550. [9] Martin DR. The laboratory diagnosis of Streptococcal pharyngitis. Throat cultures, rapid tests and streptococcal antibodies. In: Peche`re JC, Kaplan EL, editors. Streptococcal pharyngitis, vol. 3. Basel: Issues Infectious Disease; 2004. p. 75–84. [10] Paradise JL, Bluestone CD, Colborn DK, Bernard BS, Rockette HE, Kurs-Lasky M. Tonsillectomy and adenotonsillectomy for recurrent throat infection in moderately affected children. Pediatrics 2002;110: 7–15. [11] van Staaij BK, van den Akker EH, van der Heijden GJ, Schilder AG, Hoes AW. Adenotonsillectomy for upper respiratory infections: evidence based? Arch Dis Child 2005;90:19–25. [12] van den Akker EH, Rovers MM, van Staaij BK, Hoes AW, Schilder AG. Representativeness of trial populations: an example from a trial of adenotonsillectomy in children. Acta Otolaryngol 2003;123: 297–301. [13] Rosefsky JB. Tonsillectomies and adenotonsillectomies. Will the debate never be over? Pediatrics 2003;112:205. [14] Paradise JL. Effectiveness of tonsillectomy depends on stringency of indications. Electronic letter; 2005, 15 February. Available from: http://adcbmjjournals.com/cgi/letters.
G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361 [15] van Staij B. Author’s reply to: Effectiveness of tonsillectomy depends on stringency of indications. Electronic letter; 2005, 15 July. Available from: http://adcbmjjournals.com/cgi/letters. [16] Oomen KP, Rovers MM, van den Akker EH, van Staaij BK, Hoes AW, Schilder AG. Effect of adenotonsillectomy on middle ear status in children. Laryngoscope 2005;115:731–4. [17] American Academy of Family Physicians, American Academy of Otolaryngology-Head and Neck Surgery, American Academy of
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Pediatrics Subcommittee on Otitis Media with Effusion. Otitis media with effusion. Pediatrics 2004;113:1412–29. [18] American Academy of Family Physicians, American Academy of Otolaryngology-Head and Neck Surgery, American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 2004;113:1451–65. [19] Sehon SR, Stanley DE. A philosophical analysis of the evidence-based medicine debate. BMC Health Serv Res 2003;3:14–23.
Surgical treatment of acute recurrent throat infections in children§ Giovanni Motta a,1, Erik Esposito b, Sergio Motta a,*, Nicola Mansi c, Vincenzo Cappello a, Bernardino Cassiano b, Gaetano Motta d a
Institute of Otorhinolaryngology, Department of Preventive Medical Sciences, Azienda Universitaria ‘‘Ateneo Federico II’’, Via S. Pansini n.5, 80100, Naples, Italy b Department of Otorhinolaryngology, Azienda Ospedaliera Santa Maria della Pieta` di Nola, Naples, Italy c Struttura Complessa di Otorinolaringoiatria, Azienda Ospedaliera di Rilievo Nazionale Santobono-Pausillipon, Naples, Italy d Department of Otorhinolaryngology, II University of Naples, Italy Received 19 January 2010; accepted 7 November 2010 Available online 15 January 2011
Abstract Objective: The purpose of this study was to define the contribute of surgery and watchful waiting in the treatment of feverish episodes and other clinical manifestations related to acute recurrent throat infections in children. Methods: An observational, retrospective and multi-centric study was carried out on 407 subjects, aged 2–11, with a minimum two-year follow-up. Chi square test and Fisher’s test were used for the statistical analysis. Results: Watchful waiting prevented, similarly to surgery, recurrences of feverish episodes, but did not favourably impact on other clinical manifestations (respiratory obstruction, otitis media, group A beta hemolyticus streptococcus positive laboratory findings) as compared to surgery ( p < 0.001). Conclusions: The higher effectiveness of surgical treatment, as compared to watchful waiting, was documented in the study patients, considering all the clinical manifestations related to acute recurrent throat infections. # 2010 Elsevier Ireland Ltd. All rights reserved. Keywords: Acute recurrent throat infections; Children; Adeno-tonsillectomy; Watchful waiting
1. Introduction Recent Randomized Controlled Trials (RCTs) aimed to establish the effectiveness of adeno-tonsillectomy (AT) and adenoidectomy (A) in the treatment of acute recurrent throat infections and otitis media in children [1–5]. On the basis of the results obtained, ‘‘Guidelines’’ have been proposed with the aim to clearly defining the indications to surgery [6–8]. The purpose of our study was to verify the outcomes of adeno-tonsillectomy in the treatment of acute recurrent throat infections in children and to compare the therapeutic contribute of surgery and watchful waiting for feverish §
No funds were received in support of this study. * Corresponding author. Tel.: +39 081 7462988; fax: +39 081 7463592. E-mail addresses: [email protected], [email protected] (S. Motta). 1 Now retired.
episodes (FE) and other clinical manifestations related to acute recurrent throat infections.
2. Materials and methods An observational, multi-centric and retrospective study was carried out in four ENT units of the city and county of Naples, in Italy (1. University of Naples ‘‘Federico II’’; 2. 2nd University of Naples; 3. Azienda Ospedaliera Santa Maria della Pieta` di Nola; 4. Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon). Inclusion criteria for the study patients were: a positive medical history of acute recurrent throat infections, characterised by FE, associated or not to other clinical manifestations (naso-pharyngeal respiratory obstruction; ASO titre elevation; rheumatoid distant disorders; otitis media with effusion and acute recurrent otitis media), patients aged between 2 and 11, and
0385-8146/$ – see front matter # 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2010.11.002
G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361 Table 1 Distribution for gender and age of the study cases. WW = watchful waiting. Sex/age
Males Females 2–3 yy. 4–5 yy. 6–7 yy. 8–9 yy. 10–11 yy.
1st investigation
in the range of normality, regardless of the test technique used, in two measurements effected at an interval of 4–6 months during the 18 months prior to the patient being included in the research. ASO titre was evaluated in two subsequent examinations at an interval of 4–6 months from each other in the follow-up period. Cases with ASO titre reentered in the limits of the range of normal values were calculated and considered as cured. Rheumatoid disorders were studied by drawing on the necessary clinical and laboratory examinations; any resolution of rheumatoid disorders was excluded or confirmed on the basis of clinical and laboratory findings. (4) Otitis media with effusion and acute recurrent otitis media. Otitis media with effusion was to be established by clinical examination and type B tympanogram obtained at least twice in the 18 months prior to the patient’s inclusion in the research. Analysis of clinical findings was conducted at the end of follow-up. As for acute recurrent otitis media (defined as 3 episodes in the last 6 months or 4 episodes in the last year), patients with 1 acute inflammatory ear episodes in the follow-up period were considered as cured. The adeno-tonsillar volume was evaluated through a clinical examination and rhinofibroscopy in all cases, but the symptomatologic aspects were privileged as compared to objective findings for the aim of the present study. The study cases were divided into three groups (Fig. 1). The group 1 comprised 183 subjects who had undergone AT, and in whom the FE were >4 in the last year. The group 2 consisted of 177 patients who underwent AT, and in whom the FE were 4. The group 3 included 47 cases in whom FE were 4 in the last year and no surgery had been performed. This last group consisted of children whose parents had refused any indication for surgical treatment; in this group appropriate medical treatment was administered (antibiotics, non-steroid anti-inflammatory drugs, corticosteroids) at the time of inflammatory clinical recurrences. The decision to proceed to AT was taken for all cases after having unsuccessfully administered medical treatment (general and local antibiotic therapy, local corticosteroid therapy, etc.) at the time of inflammatory clinical recurrences for at least twelve months. In brief, of the 407 cases studied, 360 underwent AT and 47 formed the control group. The first investigation (Fig. 1) involved groups 1 and 2 (360 subjects consisting of 221
2nd investigation
FE > 4 183
FE 4 177
Total 360
AT 177
WW 47
Total 224
109 74 19 78 60 13 13
112 65 31 94 35 10 7
221 139 50 172 95 23 20
112 65 31 94 35 10 7
22 25 6 10 12 11 8
134 90 37 104 47 21 15
a minimum two-year follow-up. Exclusion criteria were as follows: craniofacial malformations, immunodeficiency syndromes, children who underwent adenoidectomy alone, and the existence of confirmed or not yet-defined genetic disorders. Children with 1 FE or even with 2 FE in the last year, but in whom the average FE incidence in the preceding two years had been <3 per year were not included in the study. The study involved 407 subjects (243 males and 164 females), aged between 2 and 11 (Table 1), who came consecutively for their first clinical examination to the above units between (a) 1st January and 31st December 2001, to the first three centres involved in the research, (b) from the 1st January to 31st March 2001, to the fourth centre. The present research was performed in accordance of the local institutional review board guidelines, as well as the Helsinki Declaration of 1975, revised in 1983. The outcome measures were as follows: (1) FE secondary to acute recurrent throat infections. During these episodes body temperature had to be 38 8C for at least three days. The study patients were evaluated according to the number of FE in the last year, >4 episodes or 4. As for the analysis of the results, we considered the average number of FE per year for each patient in the 24 months after surgery or first clinical observation (control group). Patients with FE < 1 for year in the two years following the treatment were considered as cured. (2) Naso-pharyngeal respiratory obstruction secondary to hyperplasia of pharyngeal lymphatic tissue. Two distinct grades of respiratory obstruction were considered: slight/moderate (frequent ‘‘colds’’ with rhinorrhea; openmouth breathing during sleep) and severe grade (continuous rhinorrhea; day and night open-mouth breathing; frequent and prolonged episodes of nocturnal apnoea). Nasal breathing was evaluated 24 months after surgery or after the first observation (control group). Patients with diurnal and night time nasal breathing in the follow-up period were considered as cured. (3) ASO titre elevation and distant disorders potentially due to GABHS (group A beta hemolyticus streptococcus) infection. ASO titre was considered as a more reliable immunologic indicator of a streptococcal infection as compared to cultural tests of pharyngo-tonsillar flora, in agreement with Martin [9]. ASO titre was esteemed an indicator of a recent GABHS infection if it had increased twice or more compared to the upper limit
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[()TD$FIG]
407 cases
FE > 4 183 cases
FE < 4 224 cases 2nd Investigation
1st Investigation
AT 183 cases (group 1)
AT 177 (group 2)
WW 47 cases (group 3)
Fig. 1. Scheme of the study, indicating the subdivision of the sample in two investigations. WW = watchful waiting; FE = feverish episodes.
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G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361
Table 2 Incidence and cure rate of clinical manifestations in the study sample in the first investigation. FE = feverish episodes; NPRO = naso-pharyngeal respiratory obstruction; EOM = otitis media with effusion; AROM = acute recurrent otitis media. NS = no significant. FE
NPRO Slight/moderate
Severe
Baseline incidence of clinical manifestations FE > 4 183/360 47.5% 33.3% 50.8% p NS <0.001 FE 4 177/360 41.8% 53.7% 49.2% Total 360 44.7% 43.3% 100% Cure rate of clinical manifestations after treatment FE > 4 155/183 95.4% 95.1% 84.7% p 0.005 NS NS FE 4 167/177 100% 93.7% 94.3% Total 322/360 97.5% 94.2% 89.4%
Abnormal ASO titre
Rheumatoid distant disorders
EOM
AROM
80.8%
67.2%
22.4%
30.6%
45.3%
<0.001 95.5%
<0.001 26.0%
<0.001 7.3%
NS 37.8%
NS 51.4%
88.0%
46.9%
15.0%
34.2%
48.3%
95.3%
67.4%
68.3%
87.5%
92.8%
NS 96.4%
NS 76.1%
0.04 100%
NS 85.1%
NS 82.4%
95.9%
69.8%
75.9%
86.2%
87.3%
Total
males and 139 females) who underwent AT but in whom FE was, respectively, >4 (group 1: 183 cases) and 4 (group 2: 177 cases). In the second investigation (Fig. 1) 224 patients were examined (134 males and 90 females) in whom 4 FE were documented in the 12 months prior to inclusion in the study and who came from groups 2, 3, respectively. More precisely, 177 cases proceeded to AT (group 2) and 47 children (group 3) made up the control group (watchful waiting). The study children were assessed every 6–12 months, for at least two years. Post-operative haemorrhagic complications were observed in 6 cases (1.6%), divided in primary (2 cases; 0.5%) and secondary (4 cases; 1.1%) haemorrhages; these haemorrhages required an adequate haemostasis in the operating room and one day of hospitalization. No complications were found in relation to the practiced medical treatments in the control group. Chi square test, with Bonferroni inequality test and Yates correction when necessary, and Fisher’s test – for
comparison of small groups – were used for the statistical analysis, assuming p < 0.05 as minimum value of statistical significance.
3. Results A complete list of the results obtained in the study patients has been reported in Tables 2 and 3. First investigation (Table 2). In the two years after intervention FE were 1 in 89.4% of cases. Children rate with FE < 1 per year in the two years following the treatment was 84.7% for FE > 4 group and 94.3% for FE 4 group ( p = 0.005). Naso-pharyngeal respiratory obstruction normalized after surgery in 95.9% of cases without any significant difference between 4 versus >4 FE cases ( p > 0.05). Abnormal ASO titre normalized in 118 out of 169 cases (69.8%) after surgery. Distant rheumatoid disorders were resolved in 75.9% of cases; this percentage resulted significantly higher
Table 3 Incidence and cure rate of clinical manifestations in the study sample in the second investigation. WW = watchful waiting; FE = feverish episodes; NPRO = naso-pharyngeal respiratory obstruction; EOM = otitis media with effusion; AROM = acute recurrent otitis media. NS = no significant. Treatment
FE 4
NPRO Slight/moderate
Baseline incidence of clinical manifestations AT 177/177 41.8% 100% WW 47/47 46.8% 100% p NS Cure rate of clinical manifestations after treatment AT 167/177 100% 94.3% WW 41/47 36.4% 87.2% p NS <0.001
Abnormal ASO titre
EOM
AROM
Severe
Total
53.7%
95.5%
25.9%
37.8%
51.4%
27.7%
74.5%
29.8%
31.9%
23.4%
<0.01
<0.001
NS
NS
<0.01
93.7%
96.4%
76.1%
85.1%
82.4%
30.8%
34.3%
28.6%
0%
9.9%
<0.001
<0.001
<0.001
<0.001
<0.001
G. Motta et al. / Auris Nasus Larynx 38 (2011) 356–361
( p = 0.04) in the group with EF 4 as compared to EF > 4 group. Resolution of inflammatory ear manifestations after AT occurred in 86.2% (otitis media with effusion: 106/123) and 87.3% (acute recurrent otitis media: 152/174) of the study patients. Second investigation (Table 3). FE were <1 per year in the two years following the treatment in 94.3% of patients operated with AT and in 87.2% of the control patients ( p > 0.05). Naso-pharyngeal respiratory obstruction normalized in a statistically higher percentage ( p < 0.001) of cases in the surgical group (96.4%) compared to the control group (34.3%). Following surgery, abnormal ASO titre normalized in a statistically higher percentage of cases (76.1%) in the surgical group ( p < 0.001) as compared to the control group (28.6%). Rheumatoid distant disorders were found in 10/177 cases (5.6%) who had to undergo AT; in all these children distant disorders completely resolved during the follow-up period. Rheumatoid disorders were not observed in the control group at the baseline. Resolution of otitis media with effusion and acute recurrent otitis media appeared to be significantly higher in the group that had undergone surgical treatment as compared to control group ( p < 0.001).
4. Discussion The aim of our investigations was primarily to evaluate the indications to AT for acute recurrent throat infections in children. In the present study we preferred to privilege the symptomatologic manifestations of adeno-tonsillar pathology (number of FE, degree of naso-pharyngeal respiratory obstruction, rheumatoid disorders, otitis media) compared with the objective findings (degree of hypertrophy of adenoids and palatine tonsils), since the number of FE could be not correlated to the size of palatine tonsils and adenoids and considering that both tonsillar and adenoideal volumes can interfere in the pathogenesis of naso-pharyngeal respiratory obstruction. The first investigation of the present study compared the findings related to the incidence of symptoms in groups with FE > 4 and 4 per year before and after surgery. The percentage rate of children in whom an improvement for the outcome measures was documented was high in both study groups, without statistically significant difference in their comparison, except for FE, for which the cure rate resulted statistically lower in group with FE > 4. In the second investigation, the obtained data showed a marked reduction in FE in the two groups of patients, albeit lower in the watchful waiting group than that observed in the surgical group, without statistically significant difference in their comparison. AT enabled high rates of success for all the clinical manifestations considered (naso-pharyngeal respiratory obstruction, ASO titre, otitis media with effusion and acute recurrent otitis media) in the study group, independently on their percentage incidence and severity at the baseline. In the control cases, on the other hand, the
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percentage rates of cured cases were disappointing in statistically significant terms – except for FE – compared to those obtained by surgical treatment. These data demonstrate how the effectiveness of one form of treatment cannot be assessed by referring to one clinical manifestation alone: obviously, a treatment option cannot be considered efficacious when it leads to, for instance, FE being cured but does not resolve otitis media and/or naso-pharyngeal respiratory obstruction or vice versa. It must be underlined that the cure rates resulted statistically higher in the surgical group, despite the watchful waiting group showed a less serious clinical picture with regard to the baseline incidence of symptomatologic manifestations. Our results differ with those of clinical trials that aimed to identify the most effective treatments for acute recurrent throat infections in childhood [3,4,10,11]. This discrepancy could depend on the partial assessment of the clinical manifestations related to acute recurrent throat infections, as also suggested by the work of Van den Akker et al. [12], and on an underestimation of the surgical outcomes in the mentioned studies, due to different methodological factors. In the study by Paradise et al. [3], the percentage of subjects who had undergone surgery but were lost to follow-up was higher (32/35%) as compared to control subjects (12/16%). The authors reported a reduction in the number of FE in control subjects in the third year of follow-up; nonetheless, 59 study cases (over one third of the operated patients) were excluded from the research because operated on urgently. In 2002 [10], Paradise et al. resumed their research in order to establishing if tonsillectomy was appropriate in cases with less severe symptoms than in the previous investigation [3]. The study showed a statistically significant reduction in the average number of significant episodes and moderate/severe episodes, and likewise in GABHS infections, in children who underwent tonsillectomy or AT versus the control subjects for the 3 years of follow-up globally considered; furthermore, in more than 20% of the control cases surgery was effected. In relation to the high number of surgical complications (7.9%), the authors maintained that benefits for patients surgically treated were moderate as compared to risks. The lack of data concerning the assessment of respiratory nasal obstruction and post-operative ear pathology in children enrolled in the 2-way trial (AT versus control) in the study of Paradise et al. [10] was also questioned by Rosefsky [13]. Van Staaij et al. assessed the effectiveness of AT in children whose recurrent pharyngeal infections or tonsil hypertrophy gave rise to moderate clinical manifestations [4]: fewer episodes of pharyngeal infections, throat infection and inflammations of the upper respiratory tracts were documented in operated subjects as compared to controls. Nevertheless, the authors asserted that surgery only affords modest benefits compared to watchful waiting. In a subsequent meta-analytical study, Van Staaij et al. [11] analyzed the results of A and AT in patients aged under 18. The effects of interventions on sleep obstructive respiratory disorders or on upper tract respiratory obstruc-
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tion were not considered. The authors concluded that A and AT lead to a further though modest reduction in the incidence of throat infection episodes and other related manifestations compared with control subjects, substantially agreeing with Paradise [3,10] about advising surgery in cases in whom the number of pharyngeal infections exceeds seven episodes in the last year [14,15]. In our opinion, on the contrary, surgical treatment could be considered appropriate even in cases with a lower number of FE, but with evidence of respiratory obstruction and/or otitis media with effusion/ acute recurrent otitis media and/or positive laboratory findings for GABHS infections. Previous investigations also questioned the effectiveness of surgery in the treatment of inflammatory ear pathology in children [5,16]. Paradise et al. [5] carried out two trials on 461 patients drawn from a series which initially consisted of 2122: on the basis of their results, they concluded that A and AT showed a limited effectiveness: 11 cases of the control subjects (11/98 = 11%) in the first trial and 17 (17/78 = 22%) in the second underwent surgery; these subjects were presumably excluded from the calculation, like those who had been ‘‘lost’’, since they had not completed the follow-up. Oomen et al. [16] stated that surgical treatment did not give any advantage as compared to controls for otitis media: in their work, only in 111/300 cases indication for surgery was dependent on otitis media, hearing impairment or upper respiratory tracts inflammatory disorders; moreover, 50/149 cases of controls (34%) underwent surgery and were excluded from the study. In two recent Clinical Practice Guideline [17,18], the American Academy of Paediatrics stated unequivocally that reservations on the usefulness of A and AT in the treatment of otitis media should not be taken into consideration if specific indications for such operations are found. Our considerations are not intended to criticize the results of the mentioned studies; they dispute, instead, the practice of extending these to the treatment of acute recurrent throat infections in children as a whole. As such, the possibilities and limits that RCTs and retrospective investigations have in this field of clinical practice should be well known and analyzed. It seems that in this respect Schon and Stanley’s remarks [19] are particularly appropriate when they state: ‘‘. . .we can now ask to what extent should physicians rely on RCTs as opposed to clinical experience or observational studies. Unlike the comparison with basic science, we cannot simply say that they are complementary and that we need both. As discussed above, observational studies essentially are clinical experience made systematic, and RCTs are observational studies subject to further controls’’.
5. Conclusions The obtained results revealed that watchful waiting, unlike surgery, did not influence significantly the clinical manifestations related to acute recurrent throat infections in
the study patients as compared to surgery, except for feverish episodes. The higher effectiveness of surgical treatment was documented in the study patients, considering all the clinical manifestations related to acute recurrent throat infections. The data of the present study dispute the practice of extending the results of RCTs to the treatment of the acute recurrent throat infections in children as a whole, supporting the need for an integration of findings obtained through different investigative methods.
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