Original Article
Retrospective Analysis of Chronic Rhinosinusitis in Patients With Cystic Fibrosis
Análisis retrospectivo de pacientes portadores de rinosinusitis crónica por fibrosis quística
Catalina Gutiérrez, Gloria Ribalta
, Isabel Largo
Corresponding author
Departamento de Otorrinolaringología, Clínica Las Condes, Santiago, Chile
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The same underlying pathophysiological process which affects the lungs also affects the PNS, where there is a thickening of mucus resulting in impaired mucociliary movement and bacterial colonisation, leading to secondary chronic sinus inflammation, with globular cell hyperplasia, squamous metaplasia, and loss of ciliated cells.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> At a macroscopic level, these factors obstruct sinus drainage leading to mucus stasis and resulting in local infection and inflammation which mostly obstructs the ostia. Secretions become trapped in the PNS, reducing gaseous exchange between the sinuses and the bloodstream and leading to increased CO<span class="elsevierStyleInf">2</span> partial pressure. This, in turn, results in mucosal oedema, decreased ciliary function, and bacterial colonisation.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> These changes translate into clinical symptoms, mainly in the form of sinonasal polyps and nasal obstruction. Thus, CRS is very common in patients with CF.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> There have been reports of involvement of the PNS in the paediatric population in over 90% of cases,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> with a high incidence of nasal polyps, ranging between 6% and 48% of patients, developing around the age of 5 years<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> according to various studies.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–13</span></a> These polyps are different from those appearing in atopic patients: they have a thin basal membrane, with no hyalinisation of the mucosa, fewer eosinophils and predominance of neutrophils and abundant acid mucin in the mucous glands.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,14</span></a> Recent publications have reported a high correlation between the germs cultured in the PNS and in bronchoalveolar lavage (BAL), thus indicating that the upper airway is often colonised by the same microorganisms as the lower airway, which subsequently damage the lung in a chronic manner, largely determining the fatal prognosis of this disease.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15–17</span></a> The bacteria most frequently isolated in the PNS of CF patients are <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> and <span class="elsevierStyleItalic">Staphylococcus aureus</span>, which are found in macrocolonies forming biofilms, providing them with a barrier against antimicrobial agents and inflammatory cells and promoting bacterial resistance.</p><p id="par0015" class="elsevierStylePara elsevierViewall">CRS is difficult to manage in general, but especially when due to CF. Once diagnosed, treatment should be based on treating the infection and maintaining patent PNS through medical treatment and/or endoscopic sinus surgery (ESS). This enables good drainage of secretions from the PNS, reducing lower airway infections secondary to their accumulation and, thus, progression of the disease.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,7,9</span></a> Therefore, otolaryngologists (ENT) play a vital role in the management of these patients and must work as a team with bronchopulmonary specialists in CF.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> However, the percentage of ENT consultations for this reason is not very high. The reason for this is thought to be that radiological findings do not always appear in conjunction with sinonasal symptoms.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,19</span></a> Furthermore, it may also be that the severity of pulmonary symptoms often makes patients prioritise attention to other clinical manifestations of the disease, thus underestimating or adapting to the sinonasal problems and not consulting for them.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,20</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The present study describes the teamwork between ENT and bronchopulmonary specialists for 17 years in 14 patients with CF.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted an observational, descriptive, retrospective study of patients with CRS due to CF, who were treated in the previous 17 years at a private clinic. For this study, we selected patients with confirmed diagnosis of CF by sweat test or genetic test, diagnosed with CRS according to the criteria of the American Academy of Otolaryngology and Head and Neck Surgery. This study was approved by the ethics committee of the clinic.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Data Collection</span><p id="par0030" class="elsevierStylePara elsevierViewall">We identified patients treated at the centre according to the criteria described previously and reviewed their medical records. The studied variables were: age, gender, age at diagnosis of CF, result of the sweat test and genetic testing if available, type of CRS (polypoid or non-polypoid), CT classification of PNS, age at the first ESS, number of surgical reinterventions, PNS and BAL cultures and history of lung transplantation.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Confirmed cases of CF were defined by a sweat test with quantitative pilocarpine from a laboratory confirming a chlorine result over 60<span class="elsevierStyleHsp" style=""></span>mEq/l. Normal sweat tests were considered for chlorine values up to 40<span class="elsevierStyleHsp" style=""></span>mEq/l and indefinite (or borderline) as 40–60<span class="elsevierStyleHsp" style=""></span>mEq/l (Gibson and Cooke technique). Diagnostic confirmation of cases by positive genetic test for CF were obtained from an independent clinical laboratory by polymerase chain reaction (PCR), study of gel electrophoresis and sequencing of the 27 exons of the CFTR gene, including 20<span class="elsevierStyleHsp" style=""></span>bp towards the 5′ and 3′ ends of each intron, which can identify 1300 alterations in the CFTR gene.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Following the criteria of the American Association of Otolaryngology, we defined the presence of CRS as 2 or more of the following signs and symptoms: mucopurulent discharge (anterior, posterior or both), nasal obstruction, pain, facial pressure or fullness, decreased olfaction for over 12 weeks and inflammation documented by one or more of the following findings: purulent mucus or oedema in the middle meatus or ethmoid region, polyps in the nasal cavity or middle meatus and/or radiological imaging tests showing inflammation of the PNS.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> We evaluated the presence of nasal polyposis through an endoscopic test performed by an otolaryngologist.</p><p id="par0045" class="elsevierStylePara elsevierViewall">We used the CT classification of PNS by Lund–Mackay to evaluate the radiological characteristics of PNS. We assigned a score from 0 to 2 (0=no abnormalities, 1=partial opacification, 2=total opacification) to each of the PNS (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal) on each side (right, left). Additionally, we assessed the ostiomeatal complex (0=unobstructed, 2=obstructed). Thus, the total score ranged from 0 to 24.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The surgical procedure performed on these patients was ESS expanded for CF, and carried out by the same otolaryngologist. The technique consisted in extending the ostium of the maxillary sinus to the bottom of the nostril, excising the corresponding portion of the inferior turbinate, along with ethmoidectomy, sphenoidectomy and opening of the frontal sinus, as appropriate in each case. Surgical reoperations were mainly for review and cleaning of the PNS with BAL for recurrence of infectious and polypoid diseases, in conjunction with pulmonary decompensation due to infection of the upper and lower airways.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">We conducted descriptive statistics for sociodemographic variables. The results are presented as percentages for nominal variables and as means and interquartile ranges for quantitative variables with nonparametric distribution.</p><p id="par0060" class="elsevierStylePara elsevierViewall">We used quartile remission with the mean Lund–Mackay score to evaluate the relationship with the presence of polyps according to the CT classification of PNS.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">A total of 14 patients with CF and CRS participated in the study, of which 64% were male. The mean age was 23 years (interquartile range [IR]: 19–27 years), ranging between 15 and 52 years.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The mean age at diagnosis of CF was 43.5 months (IR: 6–130 months). The lowest value was at 2 months and the highest value was at 18 years and 2 months. The sweat test was normal in 5/14 patients (35.7%), in the intermediate range in 1/14 patients (7.1%) and abnormal in 8/14 patients (57.1%). The mean chlorine result in the sweat test was 83.05<span class="elsevierStyleHsp" style=""></span>mEq/l (IR: 23.1–101.9<span class="elsevierStyleHsp" style=""></span>mEq/l).</p><p id="par0075" class="elsevierStylePara elsevierViewall">We studied the type of genetic mutation in 9/14 patients (64%), as described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The most frequent mutations found in this group were ΔF508 in 5 patients and M470 and R553 in 2 patients, respectively. All the patients (100%) with the ΔF508 mutation presented polyps.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">All of the patients (100%) suffered CRS symptoms as defined by the American Academy of Otolaryngology. Of these, 10/14 (71.4%) patients presented polypoid CRS and 4/14 (28.6%) patients presented non-polypoid CRS. Out of the patients with polypoid CRS, 50% presented the ΔF508 mutation. According to the CT classification by Lund–Mackay, patients with CF presented a mean score of 24 points, corresponding to the maximum score (IR: 18–24 points, with a minimum of 7 points in 1 patient). There was no significant variation in the Lund–Mackay score among patients with CRS with and without polyps (<span class="elsevierStyleItalic">P</span>=1).</p><p id="par0085" class="elsevierStylePara elsevierViewall">In total, 3/14 (21.4%) patients underwent lung transplantation, 2 of them at 13 years of age and the third at age 23.</p><p id="par0090" class="elsevierStylePara elsevierViewall">All CF patients with CRS underwent ESS. The youngest did so at 4 years of age and the eldest at 48 years of age. The mean age at which the first ESS took place was 14.5 years (IR: 13–19 years). Cultures of the PNS with BAL were taken during surgery. The most frequently isolated microorganisms were <span class="elsevierStyleItalic">P. aeruginosa</span>, <span class="elsevierStyleItalic">S. aureus</span> and <span class="elsevierStyleItalic">Streptococcus viridans</span>. The mean number of reoperations was 2 ESS (IR: 0–3).</p><p id="par0095" class="elsevierStylePara elsevierViewall">The 3 patients who underwent lung transplantation presented altered sweat test results, with only 1 of them having a genetic study available. All underwent ESS before lung transplantation and presented CRS with polyps and maximum Lund–Mackay score (24 points). One of them was reoperated on 4 occasions after the transplant. The details of the diagnosis of CF and ESS in these patients are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">The diagnosis of CF in our study group was performed by a sweat test in 8/14 patients. In those with a normal or intermediate sweat test result and in 3 patients with altered sweat test, the study was complemented by genetic testing for CF. This indicated that symptoms were prevalent in the diagnosis of CF. Therefore, it is very important to obtain a genetic study which clarifies diagnostic doubt for cases of normal sweat tests in which clinical suspicion of CF still remains. This is especially true for the Chilean population, since there is no genetic pool describing the mutational characteristics of CF within the population.</p><p id="par0105" class="elsevierStylePara elsevierViewall">As described in the literature and observed in the cases presented in this study, almost 100% of CF patients suffered CRS.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> It has been observed that there is a higher incidence of CF gene mutations in the population with CRS than in the general population.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,22,23</span></a> The presence of polyps is also related to the type of CF mutation. These are more common in patients with 2 “strong” mutations,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> especially the classic ΔF508 mutation and the G551D mutation.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,25</span></a> In our study, 100% of patients with the classic mutation presented CRS with polyps.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Regarding the diagnosis of CRS, the presence of symptoms is rare, so it is necessary to supplement the assessment with more objective tests.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,19,26,27</span></a> A study of 34 patients with CF found 20.6% of CRS according to a questionnaire, 73.5% of CRS observed by nasofibroscopy and 93.5% of CRS revealed by a CT scan of the PNS. The variation found between the images and the symptoms may be due to lesser attention being paid by these patients to sinonasal symptoms and signs compared with other, more severe, clinical manifestations of the disease. In addition, there could be an adaptation to the symptoms which decreased their discomfort and a lack of knowledge of sinonasal disease and how it can influence the quality of life and pulmonary disease progression.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,20</span></a> According to Boari, endoscopy appears to be the most sensitive method for detecting CRS, since it identifies sinonasal abnormalities despite there being no clinical suspicion of CRS. Therefore, it should be performed periodically among these patients.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> For the same reason, the contribution of otolaryngologists in the monitoring of CF is notable.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Medical management should be the first line treatment for CRS due to CF, in an attempt to restore ventilation and drainage of the sinonasal tract and improve mucociliary clearance. Ideally, cultures of the middle meatus should be taken in order to treat infections. In addition, nasal irrigation with hypertonic solutions should be performed in order to remove debris and crusts,<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28–31</span></a> and topical medication should also be applied. Unfortunately, there comes a point when inhalation therapies cease to work, so an effective treatment of sinonasal disease depends significantly on surgery.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,7,9,32</span></a> Nevertheless, ESS is not a definitive treatment for CRS and the tendency is towards relapse, with a higher frequency than in other cases of CRS.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,9,26,33,34</span></a> The aim of ESS is to extend the drainage ostium of the cavities so as to facilitate, on the one hand, a better drainage of thick secretions and, on the other hand, the entry of saline washings which patients should perform methodically. Moreover, it also aims to facilitate the taking of culture samples from the PNS operated during exacerbation periods of CRS and the access of local treatments with nebulised antibiotics.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Indications for ESS in CRS due to CF correspond to: prolonged RS unresponsive to medical treatment of at least 6 months evolution, persistent headache,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> pulmonary exacerbation associated with RS, mucocele and before lung transplantion.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Ideally, the use of a tamponade during surgery is not recommended; however, if its use becomes necessary, then this should be left for the shortest time possible and preferably removed within 24<span class="elsevierStyleHsp" style=""></span>h. Isolated polypectomy without ESS should not be done, as it is less effective.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Some studies have shown that ESS has significant benefits on CRS symptom scores and endoscopic scores.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,34,36</span></a> Orbitofrontal headache requires special attention, since it is the symptom with less improvement after surgery and may indicate recurrence of frontal mucopyocele and the presence of intracranial complications of CRS.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Given the high recurrence of CRS with or without polyps in this disease, it is only reoperated when there is an imbalance of the lower airway or when the degree of nasal obstruction prevents adequate ventilation. However, these patients often require reintervention, so it is very important to preserve the anatomical repair points, such as the middle turbinate, which guide subsequent surgeries. According to different studies, the mean time interval between surgeries is variable and ranges from 18 to 48 months.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,33</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">It has been reported that treatment of CRS is essential to reduce its negative impact on transplanted lungs for patients with CRS due to CF with lung transplants. It has been observed that a decrease in colonisation of the upper airway diminishes colonisation of the lower airway, the rate of pneumonia and tracheobronchitis and the incidence of obliterative bronchiolitis.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,37</span></a> If lung conditions permit it, ESS should be performed prior to trasplantation.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> If the patient's condition is very deteriorated, ESS will be performed after recovery from the transplantation.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Saline nasal irrigation is recommended to minimise symptoms and exacerbations of CRS and subsequent to ESS.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,30,38,39</span></a> This should be done with syringes in order to obtain a good washing of secretions,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> since nebulisers are not capable of displacing them and saline sprays only penetrate in up 3% of operated PNS.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> The benefits of nasal irrigation include improvement in mucociliary clearance, decreased oedema of the nasal mucosal and mechanical movement of debris and allergens, which in turn improve nasal function and reduce symptoms. However, the exact mechanism of action of saline washes is not clearly known.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41,42</span></a> Hypertonic saline washes have shown greater benefits than isotonic ones and especially improve mucociliary clearance.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41,43–46</span></a> Tobramycin can also be used during postoperative management in daily nasal irrigations.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Although the use of mometasone is not supported by the medical literature, in the empirical experience of the senior author, using it as an adjuvant therapy helps to reduce inflammation of the PNS and nasal passages and aids in controlling the recurrence of polyps and infection, especially in cases of CRS with polyps. After hospital discharge, ENT controls must be followed in order to obtain serial cultures: monthly during the first 6–9 postoperative months and then according to the evolution, always maintaining regular monitoring by the otolaryngologist. A count greater than or equal to 10<span class="elsevierStyleSup">4</span> colonies in PNS aspirate should be considered positive. An adequate control of infection reduces recurrences, but success depends primarily on patient adherence to daily nasal washes and regular controls.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusions</span><p id="par0140" class="elsevierStylePara elsevierViewall">A sweat test remains the test of choice for the initial diagnosis of CF in our environment due to the impossibility of carrying out genetic testing on all our patients. However, genetic testing is still indispensable in cases where the sweat test is negative or inconclusive and the symptoms are suggestive of the disease. The ideal situation would be to conduct a genetic study of all patients.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Given the high prevalence of CRS among patients with CF, all of them should undergo a CT scan of PNS during their initial assessment. This becomes even more important when we consider that germs from the PNS are precisely the ones which colonise the lower airway. Thus, otolaryngologists must be an integral part of CF teams.</p><p id="par0150" class="elsevierStylePara elsevierViewall">ESS should be performed in those patients in whom medical treatment fails to clear the PNS and infection colonises the lower airway. In addition, it is also indicated for patients who are to undergo lung transplantation or in cases of chronic headache.</p><p id="par0155" class="elsevierStylePara elsevierViewall">ESS does not follow the basic principles which apply to this surgery in classical CRS, as this must be an ESS procedure extended with large ostia which facilitate drainage of the PNS, given the lack of mucus drainage existing in CF. This type of surgery enables better nasal washings for patients and also facilitates obtaining of PNS bacterial cultures by otolaryngologists during the postoperative period in cases of CRS exacerbation.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Recurrence of sinonasal disease is very common and patients often need to be reoperated more than once. Thus, it is very important to maintain anatomical repair points, such as the middle turbinate, during the ESS intervention.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres95028" "titulo" => array:6 [ 0 => "Abstract" 1 => "Introduction" 2 => "Objective" 3 => "Method" 4 => "Results" 5 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec82180" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres95029" "titulo" => array:6 [ 0 => "Resumen" 1 => "Introducción" 2 => "Objetivo" 3 => "Método" 4 => "Resultados" 5 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec82181" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Data Collection" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Statistical Analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-12-22" "fechaAceptado" => "2012-04-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec82180" "palabras" => array:4 [ 0 => "Chronic rhinosinusitis" 1 => "Cystic fibrosis" 2 => "Endoscopic sinus surgery" 3 => "Otolaryngologist" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec82181" "palabras" => array:4 [ 0 => "Rinosinusitis crónica" 1 => "Fibrosis quística" 2 => "Cirugía endoscópica nasal" 3 => "Otorrinolaringólogo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chronic rhinosinusitis (CRS) is very common in patients with cystic fibrosis (CF). This can be explained by the unified airway concept, where the same pathophysiological phenomenon that affects the lungs, affects the paranasal sinuses (PNS). The management of these cases is difficult.</p> <span class="elsevierStyleSectionTitle">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To describe the teamwork of otolaryngologists and bronchopulmonary specialists in patients with CF.</p> <span class="elsevierStyleSectionTitle">Method</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We performed a descriptive, retrospective study over the last 17 years, which included 14 patients with CRS and CF attended at a private hospital.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Of the patients, 64% were male and the median age was 23 years. The most frequent mutations found were ΔF508, M470 and R553. All of the patients with ΔF508 mutation had nasal polyps. 100% of the patients had clinical findings of CRS. All the patients had had endoscopic nasal surgery. The median number of endoscopic surgeries was 2.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Given the high prevalence of CRS in patients with CF, everyone should have a computed tomography scan of the PNS during the initial assessment, considering that sinus germs are the ones that colonise the lower airway. The otolaryngologist should be part of the CF team. Before receiving a lung transplant or in cases of chronic headache, endoscopic surgery should be performed in patients in whom medical treatment fails to clear the sinuses because this infection is the one that colonises the lower airway.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La rinosinusitis crónica es muy frecuente en pacientes con fibrosis quística, lo que se puede explicar por el concepto de vía aérea unificada, donde el mismo fenómeno fisiopatológico que afecta a los pulmones, afecta a las cavidades paranasales. El manejo de estos casos es especialmente difícil.</p> <span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Describir el trabajo en equipo de otorrinolaringólogos y neumólogos en pacientes portadores de fibrosis quística.</p> <span class="elsevierStyleSectionTitle">Método</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio descriptivo, retrospectivo de 14 pacientes portadores de fibrosis quística con rinosinusitis crónica atendidos durante los últimos 17 años en una clínica privada.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El 64% es de sexo masculino. La mediana de la edad al punto de corte del estudio es de 23 años. Las mutaciones más frecuentes encontradas son ΔF508, M470 y R553. El 100% de los pacientes con la mutación ΔF508 presentan pólipos. El 100% de los pacientes tienen clínica de rinosinusitis crónica. Todos han sido sometidos a cirugía endoscópica. La mediana del número de reintervenciones es de 2 cirugías endoscópicas.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Dada la alta prevalencia de rinosinusitis crónica en estos pacientes, todos deberían tener una tomografía computarizada de cavidades paranasales durante su evaluación inicial considerando que son los gérmenes de las cavidades paranasales los que colonizan la vía aérea baja. El otorrinolaringólogo debe ser parte integral del equipo de fibrosis quística. La cirugía endoscópica debe realizarse en pacientes en que el tratamiento médico no logre limpiar las cavidades paranasales y sea esta infección la que esté colonizando la vía aérea inferior, antes de recibir trasplante de pulmón, o en cefalea crónica.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Gutiérrez C, et al. Análisis retrospectivo de pacientes portadores de rinosinusitis crónica por fibrosis quística. Acta Otorrinolaringol Esp. 2012;63:286–91.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">CF: cystic fibrosis; CRS: chronic rhinosinusitis.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Mutation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">CRS With Polyps \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Lund–Mackay Score \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ΔF508/M470 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ΔF508/R553 X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ΔF508/R553 X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ΔF508/F50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ΔF508/p.N1303 K \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">542X/1078 del \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">R334 W/T3515/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">997F/F834/7 T/9 T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M470V/M470 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179871.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Type of Genetic Mutation in Patients With CRS Due to CF.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CF: cystic fibrosis; CRS: chronic rhinosinusitis; ESS: endoscopic sinus surgery.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age at Diagnosis of CF, Months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Sweat Test (Chlorine), mEq/l \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Genetic Mutation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age at Transplant, Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age at First ESS, Years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Reintervention, ESS \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">101.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ΔF508/p.N1303 K \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">103.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179872.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Patients With CF and CRS and Lung Transplants.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:46 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2023 June | 1 | 0 | 1 |
| 2021 February | 0 | 1 | 1 |
| 2021 January | 0 | 2 | 2 |
| 2020 December | 0 | 3 | 3 |
| 2020 November | 0 | 3 | 3 |
| 2020 October | 0 | 1 | 1 |
| 2020 September | 0 | 1 | 1 |
| 2020 March | 8 | 7 | 15 |
| 2020 February | 19 | 8 | 27 |
| 2020 January | 16 | 4 | 20 |
| 2019 December | 15 | 9 | 24 |
| 2019 November | 14 | 12 | 26 |
| 2019 October | 10 | 2 | 12 |
| 2019 September | 6 | 6 | 12 |
| 2019 August | 14 | 8 | 22 |
| 2019 July | 11 | 19 | 30 |
| 2019 June | 11 | 27 | 38 |
| 2019 May | 61 | 36 | 97 |
| 2019 April | 24 | 23 | 47 |
| 2019 March | 6 | 4 | 10 |
| 2019 February | 7 | 11 | 18 |
| 2019 January | 11 | 9 | 20 |
| 2018 December | 4 | 9 | 13 |
| 2018 November | 18 | 2 | 20 |
| 2018 October | 4 | 2 | 6 |
| 2018 May | 0 | 1 | 1 |
| 2018 April | 9 | 1 | 10 |
| 2018 March | 11 | 1 | 12 |
| 2018 February | 8 | 0 | 8 |
| 2018 January | 13 | 1 | 14 |
| 2017 December | 1 | 0 | 1 |
| 2017 November | 9 | 2 | 11 |
| 2017 October | 15 | 4 | 19 |
| 2017 September | 10 | 9 | 19 |
| 2017 August | 12 | 5 | 17 |
| 2017 July | 20 | 6 | 26 |
| 2017 June | 13 | 18 | 31 |
| 2017 May | 12 | 21 | 33 |
| 2017 April | 23 | 9 | 32 |
| 2017 March | 11 | 21 | 32 |
| 2017 February | 8 | 5 | 13 |
| 2017 January | 14 | 1 | 15 |
| 2016 December | 17 | 8 | 25 |
| 2016 November | 18 | 11 | 29 |
| 2016 October | 23 | 6 | 29 |
| 2016 September | 4 | 7 | 11 |
| 2016 August | 20 | 11 | 31 |
| 2016 July | 21 | 3 | 24 |
| 2016 June | 14 | 8 | 22 |
| 2016 May | 21 | 20 | 41 |
| 2016 April | 25 | 20 | 45 |
| 2016 March | 23 | 14 | 37 |
| 2016 February | 21 | 18 | 39 |
| 2016 January | 23 | 20 | 43 |
| 2015 December | 22 | 15 | 37 |
| 2015 November | 16 | 20 | 36 |
| 2015 October | 12 | 16 | 28 |
| 2015 September | 13 | 12 | 25 |
| 2015 August | 11 | 6 | 17 |
| 2015 July | 11 | 6 | 17 |
| 2015 June | 8 | 3 | 11 |
| 2015 May | 10 | 5 | 15 |
| 2015 April | 18 | 11 | 29 |
| 2015 March | 23 | 11 | 34 |
| 2015 February | 17 | 4 | 21 |
| 2015 January | 31 | 8 | 39 |
| 2014 December | 48 | 10 | 58 |
| 2014 November | 18 | 3 | 21 |
| 2014 October | 33 | 5 | 38 |
| 2014 September | 43 | 4 | 47 |
| 2014 August | 33 | 9 | 42 |
| 2014 July | 23 | 3 | 26 |
| 2014 June | 13 | 2 | 15 |
| 2014 May | 7 | 3 | 10 |
| 2014 April | 14 | 4 | 18 |
| 2014 March | 22 | 3 | 25 |
| 2014 February | 10 | 5 | 15 |
| 2014 January | 9 | 6 | 15 |
| 2013 December | 7 | 5 | 12 |
| 2013 November | 8 | 8 | 16 |
| 2013 October | 14 | 9 | 23 |
| 2013 September | 9 | 6 | 15 |
| 2013 August | 8 | 2 | 10 |
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