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Borro" "autores" => array:1 [ 0 => array:2 [ "Iniciales" => "J.M." "apellidos" => "Borro" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0873215915856087?idApp=UINPBA00004E" "url" => "/08732159/0000002100000001/v0_201604141151/X0873215915856087/v0_201604141151/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "titulo" => "Bronchiectasis: A retrospective study of clinical and aetiological investigation in a general respiratory department" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "5" "paginaFinal" => "10" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Amorim, J. Bento, A.P. Vaz, I. Gomes, J. de Gracia, V. Hespanhol, A. Marques" "autores" => array:7 [ 0 => array:4 [ "Iniciales" => "A." "apellidos" => "Amorim" "email" => array:1 [ 0 => "adelinamorim@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 1 => array:3 [ "Iniciales" => "J." "apellidos" => "Bento" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 2 => array:3 [ "Iniciales" => "A.P." "apellidos" => "Vaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 3 => array:3 [ "Iniciales" => "I." "apellidos" => "Gomes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 4 => array:3 [ "Iniciales" => "J." "apellidos" => "de Gracia" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "affd" ] ] ] 5 => array:3 [ "Iniciales" => "V." "apellidos" => "Hespanhol" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 6 => array:3 [ "Iniciales" => "A." "apellidos" => "Marques" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Faculty of Medicine, University of Porto, Portugal" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Pneumology, Centro Hospitalar de S. João, EPE, Porto, Portugal" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Faculty of Medicine, Autonomous University of Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] 3 => array:3 [ "entidad" => "Pneumology, CIBER Enfermedades Respiratorias (CIBERES) Hospital Vall d’Hebron, Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "affd" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "<span class="elsevierStyleSup">*</span>" "correspondencia" => "Corresponding author. adelinamorim@gmail.com" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "420v21n01-90385609fig1.jpg" "Alto" => 1088 "Ancho" => 1526 "Tamanyo" => 211021 ] ] "descripcion" => array:1 [ "en" => "Aetiological investigation. AAT, ¿1-antitrypsin." ] ] ] "textoCompleto" => "<a name="sec0005" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStylePara">Bronchiectasis (BE) results from a large number of diseases and is associated with high morbidity and significant costs for health-care systems.<a href="#bib32" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">, </span><a href="#bib33" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a></p><p class="elsevierStylePara">For many years respiratory infections were the main identifiable cause. However, post-infectious BE has been decreasing mainly in developed countries due to vaccination programmes, antibiotic therapy and better social-hygienic conditions while other congenital or acquired causes have been described now that we have more accurate diagnosis methods.<a href="#bib34" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">3</span></a></p><p class="elsevierStylePara">In recent years, a number of studies have shown that an aetiological diagnosis can change the therapeutic approach in a relevant percentage of patients.<a href="#bib35" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib37" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a></p><p class="elsevierStylePara">Research carried out in units with great experience in BE and with specialized resources may not be typical of the assessment which is carried out in the majority of general respiratory services. There is some evidence that the study and follow-up of patients in specialized centres probably contribute to a larger number of aetiological diagnoses and more appropriate treatment.<a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib37" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a></p><p class="elsevierStylePara">The local characteristics of BE patients were unknown, namely the level of research, BE aetiologies, functional severity and microbiological characteristics.</p><p class="elsevierStylePara">The aim of this study was to evaluate how accurate and extensive the clinical and aetiological research was for BE patients followed in the pulmonology outpatient service of a central hospital which did not routinely use a thorough, pre-existing protocol for it.</p><a name="sec0010" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Materials and methods</span><p class="elsevierStylePara">A retrospective analysis of the clinical records of adult patients with BE diagnosis who were seen and managed in the pulmonology outpatient service, from January 2008 to January 2009, was carried out. The patients concerned had to be followed-up for at least 1 year.</p><p class="elsevierStylePara">The diagnosis of BE was established by the characteristic features of the high-resolution computed tomography (HRCT) of the thorax (bronchoarterial ratio ≥1, dilated bronchi visible ≤1 cm from parietal pleura, cystic changes and a lack of normal bronchial tapering) or the CT, if unequivocal evidence of BE existed.</p><p class="elsevierStylePara">Patients with CF and interstitial pathology were excluded.</p><p class="elsevierStylePara">Each pulmonologist involved was totally responsible for the clinical records, the follow-up and aetiological research, without having to comply with any predefined protocol. We arrived at an aetiological diagnosis based on the clinical records and the results of earlier diagnostic tests done by the patient's clinician. There was no subsequent research done to complement our study.</p><p class="elsevierStylePara">The demographical, clinical, functional, radiological and microbiological data were reviewed. The exams that had been performed to explain the BE aetiology, namely, the sweat test, cystic fibrosis (CF) genotyping, measurement of serum immunoglobulins (Igs), α1-antitrypsin (AAT) and the semen analysis were recorded.</p><p class="elsevierStylePara">The sweat test was performed by conductivity method and the CF genotyping test screened the 33 most frequent <span class="elsevierStyleItalic">CFTR</span> mutations in Portuguese population. In some cases a complete analysis of the <span class="elsevierStyleItalic">CFTR</span> gene was performed.</p><p class="elsevierStylePara">The respiratory function tests were done according to standard international recommendations.<a href="#bib38" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">7</span></a></p><p class="elsevierStylePara">The isolation of the same pathogen in at least 3 sputum samples, for at least one year and with a minimal interval of one month, was considered by the authors as the definition of chronic airway colonization.</p><p class="elsevierStylePara">Statistical analysis was done with SPSS 19, 2010 software program (Statistical Package for Social Sciences, SPSS Inc., Chicago, IL, USA). Descriptive statistics (mean, standard deviation) were used to summarize the data. The Kolmogorov–Sminorv test was used to analyze the distribution of variables. Variables with a normal distribution were analyzed using the student <span class="elsevierStyleItalic">t</span>-test, while in the abnormal ones the Mann–Whitney <span class="elsevierStyleItalic">U</span> test was employed. The significance level was set at <span class="elsevierStyleItalic">p</span> < 0.05.</p><p class="elsevierStylePara">The project was approved by the Ethics Committee for Local Health of the CHSJ.</p><a name="sec0015" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStylePara">The clinical records of 202 patients with BE diagnosis were reviewed.</p><p class="elsevierStylePara">The diagnosis was established by HRCT in 94% of the patients and by CT scan in the remaining patients.</p><p class="elsevierStylePara">The patients’ general characteristics are shown in <a href="#t0005" class="elsevierStyleCrossRefs">Table 1</a>.</p><p class="elsevierStylePara">Table 1. General characteristics.</p><a name="t0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Characteristics</td><td> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleBold">Sex</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span><span class="elsevierStyleBold">(%)</span></td></tr><tr align="left"><td><span class="elsevierStyleItalic">Female</span></td><td>129 (63.9)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Age, years</span> (<span class="elsevierStyleItalic">mean</span> ± <span class="elsevierStyleItalic">SD</span>)<span class="elsevierStyleItalic">, n</span> = <span class="elsevierStyleItalic">202</span></td><td>54.4 ± 15.8</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Diagnosis age</span> (<span class="elsevierStyleItalic">mean</span> ± <span class="elsevierStyleItalic">SD</span>), <span class="elsevierStyleItalic">n</span> = <span class="elsevierStyleItalic">167</span></td><td>47.4 ± 17</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Follow up, years</span> (<span class="elsevierStyleItalic">mean</span> ± <span class="elsevierStyleItalic">SD</span>), <span class="elsevierStyleItalic">n</span> = 202</td><td>5.61 ± 7.1</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Years elapsed from symptoms onset and diagnosis</span> (<span class="elsevierStyleItalic">mean</span> ± <span class="elsevierStyleItalic">SD</span>), <span class="elsevierStyleItalic">n</span> = 133</td><td>16.9 ± 15</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleBold">Smoking habits</span>, <span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span> = <span class="elsevierStyleBold">169 (%)</span></td></tr><tr align="left"><td><span class="elsevierStyleItalic">Non-smokers</span></td><td>119 (70.4)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Smokers</span></td><td>19 (11.2)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Ex-smokers</span></td><td>31 (18.3)</td></tr><tr align="left"><td colspan="2"> </td></tr><tr align="left"><td colspan="2"><span class="elsevierStyleBold">Sputum</span>, <span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span> = <span class="elsevierStyleBold">187 (%)</span></td></tr><tr align="left"><td><span class="elsevierStyleItalic">Daily</span></td><td>110 (58.8)</td></tr><tr align="left"><td>Purulent/mucopurulent</td><td>83 (75.5)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Exacerbations</span></td><td>77 (41.2)</td></tr><tr align="left"><td><span class="elsevierStyleBold">Dyspnea</span>, <span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span> = <span class="elsevierStyleBold">176 (%)</span></td><td>74.4</td></tr><tr align="left"><td><span class="elsevierStyleBold">Hemoptysis</span>, <span class="elsevierStyleItalic"><span class="elsevierStyleBold">n</span></span> = <span class="elsevierStyleBold">202 (%)</span></td><td>61 (30.2)</td></tr></table><p class="elsevierStylePara">Fertility information was missing for 40 (54.7%) of the male patients. The upper airway symptoms were also rarely mentioned, as well as, occupational exposure to toxic chemicals, family history of BE, non respiratory symptoms and consanguinity data.</p><a name="sec0020" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Radiology</span><p class="elsevierStylePara">BE had a bilateral distribution in 89% of the patients. In 6% of the cases only 1 lobe was affected and in 80.4% 4 or more lobes were affected or there were cystic changes in 2 or more lobes. The predominant morphology was cylindrical (47%), followed by cylindrical associated with cystic (34%). The lower lobes (LL) were the most frequently affected (right LL in 88% and left LL in 86%).</p><a name="sec0025" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Microbiology</span><p class="elsevierStylePara">Thirty-four patients (16.8%) did not have a record of a sputum microbiological examination.</p><p class="elsevierStylePara">Out of 168 patients with at least one sputum microbiological examination, the most frequently isolated bacteria once or intermittently was <span class="elsevierStyleItalic">Haemophilus influenzae</span> (26.8%), followed by <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> (16.7%) and <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> (14.9%).</p><p class="elsevierStylePara">Eighty-seven patients (43.1%) had done 3 or more sputum examinations during the period of one year, of which 43 (49.4%) met the chronic colonization criteria. The most commonly isolated bacteria in this set of patients was <span class="elsevierStyleItalic">P. aeruginosa</span> (81.4%), associated in 3 cases with other bacteria, followed by <span class="elsevierStyleItalic">H. influenzae</span> (9.1%) and <span class="elsevierStyleItalic">Achromobacter xylosoxidans</span> (4.7%) (<a href="#t0010" class="elsevierStyleCrossRefs">Table 2</a>).</p><p class="elsevierStylePara">Table 2. Chronic airway colonization.</p><a name="t0010" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Microbiological agent</td><td><span class="elsevierStyleItalic">n</span> = 43 (%)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span></td><td>32 (74.4)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Haemophilus influenzae</span></td><td>3 (7)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Achromobacter xylosoxidans</span></td><td>2 (4.7)</td></tr><tr align="left"><td><span class="elsevierStyleItalic">P. aeruginosa</span> + <span class="elsevierStyleItalic">Proteus mirabilis</span></td><td>1</td></tr><tr align="left"><td><span class="elsevierStyleItalic">P. aeruginosa</span> + <span class="elsevierStyleItalic">Haemophilus influenzae</span></td><td>1</td></tr><tr align="left"><td><span class="elsevierStyleItalic">P. aeruginosa</span> + <span class="elsevierStyleItalic">MRSA</span></td><td>1</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Streptococcus pneumoniae</span></td><td>1</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Enterobacter cloacae</span></td><td>1</td></tr><tr align="left"><td><span class="elsevierStyleItalic">Aspergillus fumigatus</span></td><td>1</td></tr></table><p class="elsevierStylePara">MRSA, methicilin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>.<br></br></p><p class="elsevierStylePara">Atypical mycobacteria were identified in 20 patients, corresponding to 23 different isolations, as 2 different species were isolated in 3 patients on different occasions. The species belonging to <span class="elsevierStyleItalic">Mycobacterium avium-complex</span> (MAC) were the most common (65.2%), followed by <span class="elsevierStyleItalic">M. kansasii</span> (17.4%), <span class="elsevierStyleItalic">M. gordonae</span> (8.7%), <span class="elsevierStyleItalic">M. fortuitum</span> (4.3%) and <span class="elsevierStyleItalic">M. peregrinum</span> (4.3%). In most cases (60.9%) only one positive culture was identified. Ten patients underwent treatment, 9 for MAC and 1 for <span class="elsevierStyleItalic">M. Kansasii</span> infection, of which 2 did not meet the nontuberculosis mycobacterial infection published criteria.<a href="#bib39" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">8</span></a></p><p class="elsevierStylePara">After the BE diagnosis, 5 patients had pulmonary tuberculosis (PT).</p><a name="sec0030" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Respiratory function</span><p class="elsevierStylePara">The results of the functional assessments, based on the most recent records, are presented in <a href="#t0010" class="elsevierStyleCrossRefs">Table 2</a>. Overall, the FEV1 was 65% of predicted, of which 32% had FEV1 <50%, 31% had between 50 and 70% and 37% reached >70%.</p><p class="elsevierStylePara">Thirteen percent of the patients had type II and 5% type I respiratory failure.</p><p class="elsevierStylePara">In a comparative analysis of pulmonary function of chronic and non-chronic colonized patients the figures (<a href="#t0015" class="elsevierStyleCrossRefs">Table 3</a>) showed statistically significant lower values of FVC, FEV1, FEV1/FVC ratio and RV in colonized patients. The differences between the TLC did not reach statistical significance.</p><p class="elsevierStylePara">Table 3. Pulmonary function.</p><a name="t0015" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Parameter</td><td>Total (<span class="elsevierStyleItalic">n</span> = 195)</td><td>Chronic colonized (<span class="elsevierStyleItalic">n</span> = 43)</td><td>Non-chronic colonized (<span class="elsevierStyleItalic">n</span> = 152)</td><td><span class="elsevierStyleItalic">p</span> value</td></tr><tr align="left"><td> </td><td>(liters), mean and SD<br></br>% of predicted and SD</td><td>(liters), mean and SD<br></br>% of predicted and SD</td><td>(liters), mean and SD<br></br>% of predicted and SD</td><td> </td></tr><tr align="left"><td>FVC <span class="elsevierStyleSup">a</span></td><td>2.51 ± 0.87</td><td>1.94 ± 0.75</td><td>2.67 ± 0.84</td><td><0.01</td></tr><tr align="left"><td> </td><td>84.9 ± 23.5</td><td>69.5 ± 22</td><td>89.4 ± 22.1</td><td><0.01</td></tr><tr align="left"><td>FEV1 <span class="elsevierStyleSup">b</span></td><td>1.78 ± 2.7</td><td>1.12 ± 0.48</td><td>1.74 ± 0.75</td><td><0.01</td></tr><tr align="left"><td> </td><td>65.1 ± 25.4</td><td>48.4 ± 16.2</td><td>70.1 ± 25.3</td><td><0.01</td></tr><tr align="left"><td>FEV1/FVC</td><td>63 ± 14.3</td><td>58.8 ± 11.2</td><td>64.3 ± 14.7</td><td><0.01</td></tr><tr align="left"><td>TLC <span class="elsevierStyleSup">c</span></td><td>5.02 ± 1.2</td><td>4.73 ± 1.2</td><td>5.08 ± 1.2</td><td>ns <span class="elsevierStyleSup">e</span><br></br>(0.121)</td></tr><tr align="left"><td> </td><td>101.4 ± 19.2</td><td>98.3 ± 22</td><td>102 ± 18.3</td><td>ns<br></br>(0.219)</td></tr><tr align="left"><td>RV <span class="elsevierStyleSup">d</span></td><td>2.48 ± 0.9</td><td>2.6 ± 0.93</td><td>2.41 ± 2.67</td><td>0.033</td></tr><tr align="left"><td> </td><td>137.2 ± 49.4</td><td>153.9 ± 62</td><td>132 ± 153.9</td><td>0.012</td></tr></table><p class="elsevierStylePara">a Forced vital capacity.<br></br>b Forced expiratory volume in 1 s.<br></br>c Total lung capacity.<br></br>d Residual volume.<br></br>e Not significant.<br></br></p><a name="sec0035" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Aetiological investigation</span><p class="elsevierStylePara">The exams carried out to investigate the BE aetiology are shown in <a href="#f0005" class="elsevierStyleCrossRefs">Figure 1</a>.</p><a name="f0005" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"><img src="420v21n01-90385609fig1.jpg" alt="Aetiological investigation. AAT, α1-antitrypsin."></img></p><p class="elsevierStylePara">Figure 1. Aetiological investigation. AAT, α1-antitrypsin.</p><p class="elsevierStylePara">The CF genetic analysis was performed in 34 (16.8%) of the cases, and 1 patient was found to have 1 mutation (R334W). The extensive genetic test was performed in 4.9% of the patients. One mutation (V754M) was detected in 1 of the patients and 2 mutations [G576A; R668C] were detected in another patient which after family screening was confirmed to be in <span class="elsevierStyleItalic">cis.</span> The sweat test in these patients was negative.</p><p class="elsevierStylePara">Five patients did a semen analysis, and infertility was confirmed in 3 cases (one was diagnosed as PCD and the other two were considered as of unknown cause).</p><p class="elsevierStylePara">In relation to the upper airways, 45 patients (22.3%) did nasal CT and findings were suggestive of chronic sinusitis in 24 (11.9%).</p><p class="elsevierStylePara">The aetiologies shown in <a href="#t0020" class="elsevierStyleCrossRefs">Table 4</a> were based on the clinical records and the results of the exams carried out. A definitive aetiological diagnosis was not established in 57.4% of the patients. In 30.3% BE was post-infectious, mostly secondary to tuberculosis (27.2%).</p><p class="elsevierStylePara">Table 4. Aetiological diagnosis and comparison with prospective studies.</p><a name="t0020" class="elsevierStyleCrossRefs"></a><p class="elsevierStylePara"></p><table><tr align="left"><td>Aetiology</td><td>Amorim et al. (<span class="elsevierStyleItalic">n</span> = 202) %</td><td>Pasteur et al. <span class="elsevierStyleSup">4</span> (<span class="elsevierStyleItalic">n</span> = 150) %</td><td>Shoemark et al. <span class="elsevierStyleSup">5</span> (<span class="elsevierStyleItalic">n</span> = 165) %</td><td>McShane et al. <span class="elsevierStyleSup">8</span> (<span class="elsevierStyleItalic">n</span> = 106) %</td></tr><tr align="left"><td>Unknown/idiopathic</td><td>116 (57.4)</td><td>80 (53)</td><td>43 (26)</td><td>7 (6.6)</td></tr><tr align="left"><td>Pos-infection (PT <span class="elsevierStyleSup">a</span> and others)</td><td>62 (30.3)</td><td>44 (29)</td><td>54 (32.8)</td><td>10 (9.4)</td></tr><tr align="left"><td>Primary ciliary dyskinesia</td><td>1 (<1) <span class="elsevierStyleSup">e</span></td><td>3 (1.5)</td><td>17 (10)</td><td>3 (2.8)</td></tr><tr align="left"><td>ABPA <span class="elsevierStyleSup">b</span></td><td>1 (<1)</td><td>11 (7)</td><td>13 (8)</td><td>1 (0.9)</td></tr><tr align="left"><td>Immunodeficiency</td><td>7 (3.5)</td><td>12 (8)</td><td>11 (7)</td><td>33 (31.1)</td></tr><tr align="left"><td>Intestinal inflammatory disease</td><td>1 (<1)</td><td>2 (<1)</td><td>5 (3)</td><td>2 (2.8)</td></tr><tr align="left"><td>α1-Antitrypsin deficiency</td><td>3 (1.4)</td><td>0</td><td>0</td><td>12 (11.3)</td></tr><tr align="left"><td>Young's syndrome</td><td>0</td><td>5 (3)</td><td>5 (3)</td><td>0</td></tr><tr align="left"><td>Panbronchiolitis</td><td>0</td><td>1 (1)</td><td>4 (2)</td><td>0</td></tr><tr align="left"><td>Yellow nail syndrome</td><td>0</td><td>0</td><td>4 (2)</td><td>0</td></tr><tr align="left"><td>Nodular bronchiectatic disease</td><td>2 (<1)</td><td>0</td><td>2 (1.2)</td><td>10 (9.4)</td></tr><tr align="left"><td>Autoimmune disease</td><td>3 (1.4) <span class="elsevierStyleSup">f</span></td><td>4 (3) <span class="elsevierStyleSup">f</span></td><td>3 (2) <span class="elsevierStyleSup">f</span></td><td>30 (28.3)</td></tr><tr align="left"><td>Aspiration</td><td>2 (<1)</td><td>6 (4)</td><td>2 (1)</td><td>12 (11.3)</td></tr><tr align="left"><td>CF <span class="elsevierStyleSup">c</span> /CFRD <span class="elsevierStyleSup">d</span></td><td>3 (1.4)</td><td>4 (3)</td><td>2 (1)</td><td>0</td></tr><tr align="left"><td>Congenital anatomical defects</td><td>1 (<1) <span class="elsevierStyleSup">g</span></td><td>1 (<1)</td><td>0</td><td>1 (0.9) <span class="elsevierStyleSup">h</span></td></tr><tr align="left"><td>Others</td><td> </td><td> </td><td> </td><td>3</td></tr></table><p class="elsevierStylePara">a Pulmonary tuberculosis.<br></br>b Allergic bronchopulmonary aspergillosis.<br></br>c Cystic fibrosis.<br></br>d Cystic fibrosis related disease.<br></br>e Diagnosis not based on gold standard exams.<br></br>f Rheumatoid arthritis.<br></br>g Bronchial atresia.<br></br>h Mounier–Kuhn syndrome.<br></br></p><p class="elsevierStylePara">The 7 cases of immunodeficiency include 2 IgA deficiencies (with IgG4 deficiency), 3 common variable immunodeficiencies and 2 hematologic malignancies.</p><a name="sec0040" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Discussion</span><p class="elsevierStylePara">The 202 patients in the study were followed in the pulmonology outpatient service. There was a predominance of female and non-smoker patients in the evaluated population, which is consistent with most published series.<a href="#bib40" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">, </span><a href="#bib41" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a></p><p class="elsevierStylePara">There was a long delay in diagnosis. This could be due to the lack of specificity of BE symptoms which, on many occasions, can lead to a misdiagnosis of COPD or asthma<a href="#bib42" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">, </span><a href="#bib43" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">12</span></a> with prognostic implications.<a href="#bib35" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib44" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">13</span></a></p><p class="elsevierStylePara">The patient information was recorded and follow-ups carried out without a predefined protocol, based on existing guidelines, which certainly contributed to the absence of important clinical historic data, subjective descriptions of some symptoms and the lack of appropriate investigation tests.</p><p class="elsevierStylePara">The result of the functional assessment was compatible with an obstructive pattern, as described in the literature.<a href="#bib45" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">, </span><a href="#bib46" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">15</span></a></p><p class="elsevierStylePara">The HRCT is considered the <span class="elsevierStyleItalic">gold standard</span> diagnostic test for BE and in this review it was chosen as the confirmatory diagnostic method. In most cases BE was bilateral and the predominant morphology was cylindrical, followed by cylindrical in association with cystic. This result is partly a consequence of a more generalized use of HRCT and its high sensitivity.<a href="#bib47" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">, </span><a href="#bib48" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">17</span></a></p><p class="elsevierStylePara">According to current recommendations, sputum culture should be carried out regularly.<a href="#bib41" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">, </span><a href="#bib49" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a> It was not quite clear why 115 (56.9%) patients had not had one or had fewer than 3 samples per year. This may have led to an underestimation of the real number of chronic colonizations. The bacteria most commonly isolated, intermittently or only once, was <span class="elsevierStyleItalic">H. influenzae</span> and the bacteria most frequently associated with chronic colonization was <span class="elsevierStyleItalic">P. aeruginosa</span>. The presence of the latter has been linked to greater clinical and functional severity, greater numbers of exacerbations and worse quality of life.<a href="#bib33" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib50" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">19</span></a> This fact could explain why further bacteriological sputum tests had been requested for this subset of patients, which means that <span class="elsevierStyleItalic">P. aeruginosa</span> may not be the bacteria most frequently associated with chronic colonization.</p><p class="elsevierStylePara">The pulmonary function was significantly worse in the chronic colonized patients, which reflects the severity usually associated with the chronic infection.</p><p class="elsevierStylePara">The prevalence of mycobacteria in BE patients is relatively low, ranging between 2% and 10%.<a href="#bib51" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">, </span><a href="#bib52" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">21</span></a> In this series the prevalence was in this range, MAC being the most common.<a href="#bib53" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">22</span></a></p><p class="elsevierStylePara">The assessment of BE patients must always include the investigation of the primary cause.<a href="#bib41" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">, </span><a href="#bib49" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">, </span><a href="#bib54" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">23</span></a></p><p class="elsevierStylePara"><a href="#f0005" class="elsevierStyleCrossRefs">Figure 1</a> shows the diagnostic tests carried out in total patients and in the cases of BE of unknown cause. The percentage of tests done is similar between the two groups, which suggests that further research could be done, using our local resources.</p><p class="elsevierStylePara">According to current recommendations, a conductivity sweat test value >60 mmol/l should be confirmed by chloride measurement<a href="#bib55" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">24</span></a>; this is not available in our hospital.</p><p class="elsevierStylePara">The CF genetic test allowed the detection of mutations in 3 patients who were considered to have a CFTR-related disorder because the sweat test was negative and only one mutation or two mutations in cis were detected.<a href="#bib56" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">, </span><a href="#bib57" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">26</span></a> However, to exclude CF with accuracy the quantitative sweat test should have been carried out on these patients and, if necessary, the nasal potential difference, which is not done in our country.</p><p class="elsevierStylePara">In this review, an aetiological diagnosis was obtained in 42.1% (<a href="#t0020" class="elsevierStyleCrossRefs">Table 4</a>) and the post-infectious cause was the most common, like other published series.<a href="#bib33" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">, </span><a href="#bib45" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">, </span><a href="#bib58" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">27</span></a> Compared with studies in which a diagnostic algorithm was applied prospectively (<a href="#t0020" class="elsevierStyleCrossRefs">Table 4</a>) our result is lower.<a href="#bib35" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib59" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">28</span></a></p><p class="elsevierStylePara">COPD was not considered as a cause of BE, despite the fact that some studies have shown an unexpectedly high incidence of BE in this disease.<a href="#bib59" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleSup">, </span><a href="#bib60" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">29</span></a><span class="elsevierStyleSup">, </span><a href="#bib61" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">30</span></a><span class="elsevierStyleSup">, </span><a href="#bib62" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">31</span></a> In light of current knowledge,<a href="#bib41" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a> BE associated with COPD should only be established after a careful aetiological work-up to exclude other associated diseases.</p><p class="elsevierStylePara">The reduced percentage or even absence of some pathologies in our study, namely ABPA, immunodeficiency and PCD<a href="#bib35" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">, </span><a href="#bib36" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">, </span><a href="#bib37" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">6</span></a> suggest that the implementation of an algorithmic investigation and the availability of specific tests could facilitate the achievement of rare and/or complex diagnosis.</p><a name="sec0045" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conclusion</span><p class="elsevierStylePara">In the recent years there has been a resurgence of interest in BE and it is urgent to set out our practice in the latest existing guidelines and to review our standards of care.</p><p class="elsevierStylePara">In our country there are no specialized centres for BE; not even in central hospitals.</p><p class="elsevierStylePara">As BE can result from several diseases, a detailed clinical history and physical examination is fundamental in order to establish the diagnostic hypothesis and to guide the research in the most appropriate way.</p><p class="elsevierStylePara">Our results show how important, useful clinical and aetiological findings could be missed when a pre-existing protocol is not being used. If the investigation and medical follow-ups were done with a pre-defined protocol based on current published guidelines,<a href="#bib41" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">, </span><a href="#bib49" class="elsevierStyleCrossRefs"><span class="elsevierStyleSup">18</span></a> we would probably have a higher percentage of accurate diagnoses and a better clinical characterization of the patients.</p><p class="elsevierStylePara">The establishment of dedicated outpatient clinics may help to improve the global management of these patients, from diagnosis to therapeutic interventions, and consequently improve prognosis and understanding of the natural course of the disease.</p><a name="sec0050" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Ethical disclosures</span><a name="sec0055" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Protection of human and animal subjects</span><p class="elsevierStylePara">The authors declare that no experiments were performed on humans or animals for this study.</p><a name="sec0060" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Confidentiality of data</span><p class="elsevierStylePara">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p><a name="sec0065" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p class="elsevierStylePara">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document</p><a name="sec0070" class="elsevierStyleCrossRefs"></a><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p class="elsevierStylePara">Dr. Javier de Gracia declare the following conflicts of interest: received industry-sponsored grand funding from Grifolds, Gilead, Novartis for participating in clinical trials and received fees for lectures and other educational activities from Praxis.</p><p class="elsevierStylePara">Acknowledgements</p><p class="elsevierStylePara">I would like to thank the collaboration of all colleagues from the Pneumology Service who referred patients, accompanied in outpatient care, to be included in the investigation.</p><p class="elsevierStylePara">Received 12 November 2013 <br></br>Accepted 15 June 2014 </p><p class="elsevierStylePara">Corresponding author. adelinamorim@gmail.com</p>" "pdfFichero" => "320v21n01a90385610pdf001.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec640997" "palabras" => array:5 [ 0 => "Adult" 1 => "Bronchiectasis" 2 => "Clinical investigation" 3 => "Aetiology" 4 => "Respiratory service" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle"> Background</span><br/><p class="elsevierStylePara"> Bronchiectasis can result from many diseases, which makes the aetiological investigation a complex process demanding special resources and experience. The aetiological diagnosis has been proven to be useful for the therapeutic approach.</p><span class="elsevierStyleSectionTitle"> Objective</span><br/><p class="elsevierStylePara"> Evaluate how accurately and extensive the clinical and aetiological research was for adult bronchiectasis patients in pulmonology outpatient service which were not following a pre-existing protocol.</p><span class="elsevierStyleSectionTitle"> Methods</span><br/><p class="elsevierStylePara"> We retrospectively reviewed the records of 202 adult patients with bronchiectasis, including the examinations performed to explain the aetiology.</p><span class="elsevierStyleSectionTitle"> Results</span><br/><p class="elsevierStylePara"> The mean age of the patients was 54 ± 15 years, there was a predominance of female (63.9%) and non-smoker (70%) patients. Functional evaluation showed a mild airway obstruction.</p><p class="elsevierStylePara"> The sputum microbiological examination was available for 168 patients (43.1% had 3 or more sputum examinations during one year). Immunoglobulins and α1-antitrypsin were measured in around 50% of the patients. The sweat test and the CF genotyping test were performed in 18% and 17% of the patients, respectively.</p><p class="elsevierStylePara"> The most commonly identified cause was post-infectious (30.3%), mostly tuberculosis (27.2%). No definitive aetiological diagnosis was established in 57.4% of the patients. We achieved a lower aetiological diagnosis if we compare our series with studies in which a diagnostic algorithm was applied prospectively.</p><span class="elsevierStyleSectionTitle"> Conclusions</span><br/><p class="elsevierStylePara"> The general characteristics of our patients were similar with other series. Detailed investigation of bronchiectasis is not a standard practice in our outpatient service. These results suggest that the use of a predefined protocol, based on current guidelines, could improve the assessment of these patients and facilitate the achievement of a definitive aetiology.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "420v21n01-90385609fig1.jpg" "Alto" => 1088 "Ancho" => 1526 "Tamanyo" => 211021 ] ] "descripcion" => array:1 [ "en" => "Aetiological investigation. AAT, ¿1-antitrypsin." ] ] 1 => array:6 [ "identificador" => "fig2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "descripcion" => array:1 [ "en" => "Aetiological investigation. AAT, α1-antitrypsin." ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib32" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Prevalence and economic burden of bronchiectasis. Clin Pulm Med. 2005; 12:205-9." "contribucion" => array:1 [ 0 => array:3 [ "titulo" => "Prevalence and economic burden of bronchiectasis." "idioma" => "en" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Weycker D" 1 => "Edelsberg J" 2 => "Oster G" 3 => "Tino G." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Pulm Med. 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Year/Month | Html | Total | |
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2024 November | 10 | 4 | 14 |
2024 October | 70 | 46 | 116 |
2024 September | 91 | 48 | 139 |
2024 August | 127 | 50 | 177 |
2024 July | 110 | 52 | 162 |
2024 June | 114 | 28 | 142 |
2024 May | 76 | 32 | 108 |
2024 April | 85 | 49 | 134 |
2024 March | 80 | 29 | 109 |
2024 February | 75 | 23 | 98 |
2024 January | 78 | 34 | 112 |
2023 December | 56 | 34 | 90 |
2023 November | 82 | 45 | 127 |
2023 October | 70 | 43 | 113 |
2023 September | 66 | 42 | 108 |
2023 August | 43 | 17 | 60 |
2023 July | 59 | 35 | 94 |
2023 June | 55 | 21 | 76 |
2023 May | 97 | 31 | 128 |
2023 April | 79 | 30 | 109 |
2023 March | 141 | 26 | 167 |
2023 February | 109 | 30 | 139 |
2023 January | 48 | 22 | 70 |
2022 December | 79 | 25 | 104 |
2022 November | 118 | 37 | 155 |
2022 October | 108 | 43 | 151 |
2022 September | 52 | 34 | 86 |
2022 August | 85 | 51 | 136 |
2022 July | 78 | 52 | 130 |
2022 June | 70 | 58 | 128 |
2022 May | 65 | 39 | 104 |
2022 April | 48 | 35 | 83 |
2022 March | 50 | 45 | 95 |
2022 February | 56 | 31 | 87 |
2022 January | 48 | 34 | 82 |
2021 December | 23 | 32 | 55 |
2021 November | 40 | 38 | 78 |
2021 October | 50 | 41 | 91 |
2021 September | 37 | 30 | 67 |
2021 August | 33 | 31 | 64 |
2021 July | 39 | 32 | 71 |
2021 June | 50 | 32 | 82 |
2021 May | 76 | 29 | 105 |
2021 April | 86 | 75 | 161 |
2021 March | 88 | 19 | 107 |
2021 February | 101 | 25 | 126 |
2021 January | 53 | 22 | 75 |
2020 December | 34 | 9 | 43 |
2020 November | 44 | 22 | 66 |
2020 October | 35 | 17 | 52 |
2020 September | 58 | 26 | 84 |
2020 August | 76 | 26 | 102 |
2020 July | 76 | 22 | 98 |
2020 June | 63 | 15 | 78 |
2020 May | 61 | 20 | 81 |
2020 April | 58 | 14 | 72 |
2020 March | 48 | 12 | 60 |
2020 February | 56 | 20 | 76 |
2020 January | 53 | 12 | 65 |
2019 December | 58 | 26 | 84 |
2019 November | 67 | 17 | 84 |
2019 October | 65 | 25 | 90 |
2019 September | 55 | 19 | 74 |
2019 August | 297 | 19 | 316 |
2019 July | 327 | 13 | 340 |
2019 June | 340 | 10 | 350 |
2019 May | 292 | 14 | 306 |
2019 April | 293 | 24 | 317 |
2019 March | 445 | 16 | 461 |
2019 February | 395 | 8 | 403 |
2019 January | 422 | 26 | 448 |
2018 December | 113 | 9 | 122 |
2018 November | 92 | 0 | 92 |
2018 October | 133 | 14 | 147 |
2018 September | 41 | 4 | 45 |
2018 August | 40 | 70 | 110 |
2018 July | 49 | 15 | 64 |
2018 June | 70 | 20 | 90 |
2018 May | 135 | 17 | 152 |
2018 April | 78 | 19 | 97 |
2018 March | 132 | 25 | 157 |
2018 February | 53 | 11 | 64 |
2018 January | 117 | 14 | 131 |
2017 December | 181 | 20 | 201 |
2017 November | 62 | 14 | 76 |
2017 October | 10 | 14 | 24 |
2017 September | 21 | 14 | 35 |
2017 August | 21 | 21 | 42 |
2017 July | 17 | 14 | 31 |
2017 June | 20 | 18 | 38 |
2017 May | 24 | 18 | 42 |
2017 April | 8 | 5 | 13 |
2017 March | 10 | 5 | 15 |
2017 February | 4 | 5 | 9 |
2017 January | 13 | 12 | 25 |
2016 December | 6 | 6 | 12 |
2016 November | 9 | 5 | 14 |
2016 October | 1 | 4 | 5 |
2016 September | 2 | 2 | 4 |
2016 August | 4 | 5 | 9 |
2016 July | 5 | 8 | 13 |
2016 June | 2 | 8 | 10 |
2016 May | 6 | 3 | 9 |
2016 April | 27 | 3 | 30 |
2016 March | 46 | 29 | 75 |
2016 February | 37 | 42 | 79 |
2016 January | 21 | 33 | 54 |
2015 December | 25 | 23 | 48 |
2015 November | 30 | 22 | 52 |
2015 October | 24 | 26 | 50 |
2015 September | 25 | 25 | 50 |
2015 August | 20 | 17 | 37 |
2015 July | 25 | 6 | 31 |
2015 June | 13 | 11 | 24 |
2015 May | 44 | 19 | 63 |
2015 April | 56 | 33 | 89 |
2015 March | 108 | 60 | 168 |
2015 February | 8 | 80 | 88 |