HU In Patients Research Articles

The impact of cancer prehabilitation on psychological outcomes and quality of life in patients with gastro-oesophageal cancer.

e16096 Background: The impact of cancer on psychological health and health related quality of life (HRQoL) is complex and involves an interaction between pre-existing and cancer related psychological morbidity and symptoms. Factors such as self-efficacy are known predictors of recovery and HRQoL. The aim of this study is to assess the impact of multi-modal personalised prehabilitation on psychological outcomes and HRQoL in patients with curable oesophageal and gastric (OG) cancer. Methods: Data was collected for to all patients treated at a specialist centre between Jan 2016 and June 2018. Patients received multi-modal (physical, nutrition and psychological) prehabilitation from diagnosis into the post-operative period. Data on self-efficacy (SE), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and HRQoL (European Organization for Research and treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) were collected at diagnosis (T1), completion of neo-adjuvant chemotherapy (T2) and 3 months after surgery (T3). A previously validated mapping function was used for predicting Euro QoL 5D-3L (EQ-5D-3L) from scale scores of the EORTC QLQ-C30 instrument to derive a EQ health utility (EQ-HU). Results: 137 patients underwent surgery. 86 patients underwent a thoracotomy in addition to a laparotomy. 107 patients received neo-adjuvant treatment. There was a significant improvement in SE [8.2 (6.2-9) to 8.8 (7.8-9.7); p = 0.002] and anxiety [5 (3-8) to 4 (2,7); p = 0.04] but not depression [2 (1-5) to 3 (1-5); p = 0.26] between T1 and T2. There were no differences between T2 and T3. There were no differences in global HRQoL and the individual scales of the EORTC QLQ-C30 between T1 and T2. However, between T2 and T3, there were significant reductions in global HRQoL [69.6 (18.2) to 64.7 (20.9); p = 0.04], physical [83.2 (18.2) to 70.9 (20.5); p = 0.001], role [79 (28.6) to 70.9 (28.3; p = 0.02], cognitive [84.2 (22.3) to 76 (23.3); p = 0.004] and social [79 (24.2) to 65.5 (26.1); p = 0.001] but not emotional functions [80.1 (21.4) to 79.5 (23.3); p = 0.67]. Mapping revealed that there was a significant improvement in EQ-HU from T1 to T2 [0.54 (0.52) to 0.79 (0.34); p = 0.001] and a significant fall from T2 to T3 [ 0.79 (0.34) to 0.58 (0.44); p = 0.001]. The minimum and maximum predicted values matched those of the validated mapping function used. Conclusions: This study shows that prehabilitation can have a significant impact on HU in patients on chemotherapy. Despite the well-recognised limitations of mapping, HU at baseline was comparable to that shown in previous research in OG cancer patients. Reduction in HRQoL seen after surgery was much less than previously published research, suggesting the protective effect of prehabilitation. Physical function deterioration, in particular was much less than anticipated.

Management of Renal Dysfunctions in Escort-HU Study

▪BACKGROUNDRenal impairment is a progressive chronic complication of sickle cell disease (SCD) that begins in childhood and may progress until renal failure. It is responsible for mortality in 12% of SS SCD adults (Tehseen S, 2017).Causes of renal damages in SCD patients are multiple: hemolysis, vaso-occlusive episodes which lead to renal injuries, papillary necrosis, medullary fibrosis and focal segmental glomerulosclerosis (Rees D, 2010).Hydroxycarbamide (hydroxyurea or HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and authorized since 2007 in Europe as an orphan medicinal product for the prevention of recurrent vaso-occlusive crises and acute chest syndrome in adults and children older than 2 years with SCD. HU also seems to protect kidney function in SCD by decreasing proteinuria (Bartolucci P, 2015).As renal excretion is a pathway of HU elimination (60% of dose excreted in urine), consideration should be given to decrease the dose of HU in patients with renal impairment.We propose to study SCD patients with renal diseases treated with hydroxycarbamide (Siklos) and enrolled in ESCORT-HU (European Sickle Cell Disease COhoRT - HydroxyUrea), European multicenter prospective non interventional study.METHODSFrom January 2009 to June 2017, 1841 patients were enrolled in the ESCORT-HU study. 1016 patients were adults and 824 were children (1 date of birth missing). Among them, renal lesions have been reported in the study database in 220 patients (194 adults, 25 children, 1 date of birth missing).At inclusion the renal status of patients are reported in the electronic Case Report Form (e-CRF) using different clinical approaches. It allows to distinguish patients with a medical history of renal impairment (i.e. patient with renal insufficiency of etiology not reported, with an irreversible and progressive reduction in renal function) from patients with a history of sickle cell (SC) nephropathy (patients with any renal alteration related to SCD and not necessarily irreversible and progressive).RESULTSCompared to the global cohort without any kidney involvement, patients with renal lesions were older (35.8 years vs 21.0 years) as expected, with less children (11.4% vs 50.2%) and mainly with SS genotype (94.5% vs 82.2%) (Table 1).64.1% of patients with renal lesions were already treated with HU other than Siklos before their enrollment in the study, in line with the fact that kidney lesions are correlated with the ageing of the SCD population.HU was initially prescribed at lower doses in SCD patients with renal disease and naïve of HU treatment as recommended. For patients already treated with HU other than Siklos (the dose at enrolment ~ maintenance dose), even if we observed an increase of the dose until maintenance dose, this subpopulation received HU at lower daily doses (Table 2).SCD Patients with kidney diseases reported more frequent and more severe adverse events not related to SCD (AENOTSCD) than patients without renal lesions (2.30 AE per patient vs 1.49 AE per patients and 15.4% of severe AE vs 11.2%) (Figure 1). However these events are less serious (15% of serious AE vs 25% in patients without renal lesions) (Figure 2). Similarly, when focusing on AENOTSCD causally related to HU (as judged by the investigators), patients with renal lesions reported more AE especially in patients with history of renal impairment.As recommended by some guidelines (Habibi 2015, Sharpe 2014), renin-angiotensin system (RAS) inhibitors may be used is SCD patients with renal damage in order to limit the kidney disease progression. In ESCORT-HU study, RAS inhibitors were used in 47.3% of patients with renal lesions whereas it was used in 3.0% of patients without renal lesions. Consistently RAS inhibitors are mainly used in patients with a history of SCD nephropathy (54.54% vs 21.15% in the population with renal impairment) probably because damages in this subpopulation were irreversible (Table 3).CONCLUSION12% of SCD patients, mainly adults, enrolled in the ESCORT-HU study had renal dysfunctions at enrolment. As expected this subpopulation is older than the global population of the cohort. Although HU is prescribed at lower doses, these patients go on to have more adverse events and this justifies a close monitoring of them. Controlled trials are required to evaluate the role of HU on the renal failure. [Display omitted] DisclosuresBartolucci:Novartis US: Membership on an entity's Board of Directors or advisory committees; Addmedica: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; Fondation Fabre: Research Funding. Ribeil:Addmedica: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lobitz:Addmedica: Membership on an entity's Board of Directors or advisory committees. Galacteros:Addmedica: Membership on an entity's Board of Directors or advisory committees.

Lung density in the trajectory path is a strong indicator of patients sustaining a pneumothorax during CT-guided lung biopsy.

The purpose is to evaluate the prognostic significance of lung parenchymal density during percutaneous coaxial cutting needle lung biopsy (PNLB). Retrospective analysis of 179 consecutive patients (106 males, 73 females; mean age 59.16 ± 16.34 years) undergoing PNLB was included. Mean lobar parenchymal lung density, mean densities anterior to the lesion and posterior to the chest wall in the needle trajectory path were measured in HU. Lesion location and needle trajectory were also measured. Fisher's exact test and Chi-square test were conducted to analyze the categorical variables. ANOVA test was done to examine continuous and normally distributed variables. Statistical significance was considered when p < 0.05. Mean lobar parenchymal lung density (p < 0.05) and mean parenchymal lung density relative to the needle trajectory path were below -800 HU in patients who sustained a pneumothorax. Increase in the number of pleural passes was significantly associated with the risk of patients having pneumothorax (p < 0.05). The mean distance from the skin to the lesion and needle trajectory angle were not statistically different among patients with and without pneumothorax (p > 0.05). Lobar parenchymal density and lung parenchymal density anterior to the lesion and posterior to the chest wall in the needle trajectory path could be used as predicting parameters in patients undergoing PNLB who sustained a pneumothorax. These findings can help interventional radiologist further assess risk of pneumothorax when preforming such procedure.

Computed Tomography Number Changes of Gross Tumor Volume with MVCT Scans in Tomotherapy May Detect Early the Radiosensitivity of Non–small Cell Lung Cancer Patients

Evidences have showed that the computed tomography number (CTN) for tumor and certain normal structures can change after irradiation. We explored whether CTN changes of gross tumor volume with MVCT scans in Tomotherapy may be an early indicator for the radiosensitivity of NSCLC patients. Patients with stage I to III non-small cell lung cancer were eligible in this prospective study. MVCT scans were acquired during tomotherapy. The distribution of CTN and the mean values from the first treatment to the 15th treatment were collected based on the GTV generated on daily MVCT. The dose-response curve for decreased CTN of patients was quantified using the slope of a linear regression. The CTN decreased per Gy ( ΔHU/Gy ) for each patient was calculated after the 15th tomotherapy. Follow-up CT was taken after the whole radiation therapy completed, based on which the post-treatment tumor responses were assessed by two thoracic radiologists. According to the tumor responses, a cut-off value for ΔHU/Gy was calculated by SPSS software. From Jun. 2015 to Dec. 2016, 32 eligible patients were enrolled in this study. Males: 19 (60%), Females: 13 (40%), median age: 61.7 years (range 43.3-70.9). The median radiation dose was 60Gy (range 54-63Gy). In the whole group, the mean CTN was decreased by 37.35 ± 27.07 HU from the first treatment to the 15th treatment. The mean GTV was reduced by 10.26 ± 10.15 cm3. The CTN decreased per Gy (ΔHU/Gy) was ranged from 0.37 to 2.37 among all patients. Seven patients (21.9%) reached CR, 18 patients (56.2%) reached PR, and 7 patients (21.9%) reached SD after the complete tomotherapy. The mean CTN reduction ranged from 28.1 HU to 64.0 HU in patients whose post-treatment tumor responses were CR or PR and the CTN changes were linearly correlated with the radiation dose (R2= 0.87，p＜0.001). The mean CTN changes in the left 7 patients were ranged from 9.9 HU to 26.2 HU. The cut off value for ΔHU/Gy was 0.97, above which patients could have a better radiosensitivity and a further favorable post-treatment tumor response. On an early and quantitative scale, the CTN changes of MVCT in tomotherapy may early detect the radiosensitivity of NSCLC patients. Further studies included larger numbers of patients are expected to validate such a finding and explore whether CTN changes of MVCT hold the potential to optimize treatment by adjusting radiation intensity or modifying the therapeutic regimen, based on the observed radiosensitivity of patients.

PUB037 Computed Tomography Number Changes of Gross Tumor Volume with MVCT Scans in Tomotherapy May Early Detect the Radiosensitivity of NSCLC Patients

Evidences have showed that the CT number (CTN) for tumor and certain normal tissues can change after irradiation, and the CTN change may be an early indicator for radiosensitivity of NSCLC patients. Patients with stage I to III non-small cell lung cancer were eligible in this prospective study. MVCT scans were acquired during tomotherapy. The distribution of CTN and the mean values from the first treatment to the 15th treatment were collected based on the GTV generated on daily MVCT. The dose-response curve for decreased CTN of patients was quantified using the slope of a linear regression. The CTN decreased per Gy (ΔHU/Gy) for each patient was calculated after the 15th tomotherapy. Follow-up CT was taken after the whole radiation therapy completed, based on which the post-treatment tumor responses were assessed by two thoracic radiologists. According to the tumor responses, a cut-off value for ΔHU/Gy was calculated by SPSS software. From Jun. 2015 to Dec. 2015, 32 eligible patients were enrolled in this study. Males: 19 (60%), Females: 13 (40%), median age: 61.7 years (range 43.3-70.9). The median radiation dose was 60Gy (range 54-63Gy). In the whole group, the mean CTN was decreased by 37.35 ± 27.07 HU from the first treatment to the 15th treatment. The mean GTV was reduced by 10.26 ± 10.15 cm3. The CTN decreased per Gy (ΔHU/Gy) was ranged from 0.37 to 2.37 among all patients. Seven patients (21.9%) reached CR, 18 patients (56.2%) reached PR, and 7 patients (21.9%) reached SD after the complete tomotherapy. The mean CTN reduction ranged from 28.1 HU to 64.0 HU in patients whose post-treatment tumor responses were CR or PR and the CTN changes were linearly correlated with the radiation dose (R2= 0.87, p＜0.001). The mean CTN changes in the left 7 patients were ranged from 9.9 HU to 26.2 HU. The cut off value for ΔHU/Gy was 0.97, above which patients could have a better radiosensitivity and a further favorable post-treatment tumor response. On an early and quantitative scale, the CTN changes of MVCT in tomotherapy may early detect the radiosensitivity of NSCLC patients. Further studies included larger numbers of patients are expected to validate such a finding and explore whether CTN changes of MVCT hold the potential to optimize treatment by adjusting radiation intensity or modifying the therapeutic regimen, based on the observed radiosensitivity of patients.

Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ(+) thalassemia with IVS1-5(G→C) mutation.

Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation. We registered 318 patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group-I: 37 children and Group-II: 67 adults) with ≥2 years of hydroxyurea treatment were studied. The rate of vaso-occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group-I and 3 to 0, 1 to 0 and 0.5 to 0 in Group-II respectively after HU therapy (P < 0.0001). %HbF level, hemoglobin, MCV and MCH increased significantly, whereas HbS, WBC, platelet count, serum-bilirubin and LDH levels decreased significantly after HU therapy. It has been observed that along with fairly subtle hematological changes following HU therapy, there was a substantial clinical improvement occurred in these patients. Transient myelotoxicity was observed in 4.8%. There was minimal gonadal toxicity without affecting reproductive function. In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSβ(+) -thalassemia in resource poor setting.

Prolonged Administration of Hydroxyurea Reduces Morbidity and Mortality in Adult Patients with Sickle-Cell Syndromes: Long-Term Experience of a Single Center.

Hydroxycarbamide (hydroxyurea; HU) is now considered as the main pharmacological agent capable to prevent the painful crises, to reduce the frequency and length of hospital admissions, and to improve the quality of life of patients with sickle-cell disease (SCD); whether HU can prevent the severe chronic complications or modify the mortality of these patients remains still an interesting unresolved question. The present study aims to evaluate the above effects of HU in a large number of SCD patients who received HU over long period of time and were followed in a single Center. To this effect, we evaluated the records of 330 patients with SCD who have been followed in the Thalassemia Center of Laikon Hospital over the last twenty years (136M/194F; median age: 42 years, range: 20- 76 years); 34 with homozygous HbS (SS) and 296 compound heterozygotes for HbS and beta-thalassemia. Of the latter, 131 patients had HbS/beta0-thal and 165 HbS/beta+-thal (107 with the IVSI-110 and 58 with the IVSI-6 thalassemic mutation). Administration of HU was started as early as 1991; progressively, the total number of patients who received HU reached 131 (“group A”); the remaining 199 were treated conventionally (“group B”). The mean age of the patients in the two groups was similar (mean ±SD: 43.3±9.9 years for group A and 44.1±12.6 years for group B) as well as the levels of HbF. The usual dosage of HU was 20 mg/kg/day, except for some patients, where toxicity or lack of effectiveness imposed modifications of the dosage in the range of 15 to 35 mg/kg/day. The median follow-up period was 8 years (range: 0.1–17 years) for the patients who received HU and 5 years (range: 0.1–18 years) for those who did not receive HU. Apart rare exceptions, patients reported every 4–8 weeks to the Outpatient Clinic, where they had a thorough clinical and laboratory evaluation, including FBC and reticulocytes, LDH, bilirubin, other basic biochemistries and HbF using conventional techniques. The percentage of HbS/HbS, HbS/beta0-thal, and HbS/IVSI-110 patients who were given HU was 70%, 49% and 40% respectively; in contrast, very few HbS/IVSI-6 compound heterozygotes had symptoms justifying use of the drug (3.6%). Patients receiving HU showed a dramatic reduction of the frequency of severe painful crises (from 7.4±6.5 episodes per year pre-HU to 0.2±0.4 episodes post-HU; p<0.001) along with a significant reduction of transfusion requirements (mean number of administered packed red cell units: 1.5±5.9 per year pre-HU diminishing to almost zero during HU treatment; p<0.001). These results led to a significant reduction of hospital admissions from 2.1±2.9 per year pre-HU to 0.06±0.02 per year post-HU (p<0.001). Moreover, we noticed a significant reduction of the frequency of chest syndrome from 6.1% pre-HU to 0.8% during the HU period (p=0.013). In contrast, we failed to observe any significant differences in the frequency of aseptic avascular necrosis (p=0.219) or cerebrovascular episodes among the patients who received and those who did not receive HU (p=0.65). Importantly, the death rate in the group of patients receiving HU was significantly lower than that observed among patients who were conventionally treated (12 deaths in group A vs. 47 in group B; 9.1% vs. 23.6%, respectively; p=0.001). The probability of 10-year survival was 91% for the patients treated with HU, while that of the patients conventionally treated was only 70% (Figure). This difference is further magnified if one considers that prior to starting HU the patients of group A had significantly higher transfusion requirements, frequency of painful crises, yearly number of admissions to hospital and intensity of hemolysis in comparison to the group of patients who were not given HU (p=0.004, <0.001, <0.001, and 0.01, respectively). Factors that predicted for a superior survival in the HU group include the increased level of total hemoglobin, a reduced platelet and leukocyte count, increased HbF levels, low reticulocyte counts and low bilirubin and serum LDH levels at 6 months post-HU administration. Side-effects of HU therapy were minimal, predictable and easily manageable. Our study provides evidence that, in addition to reducing the number of painful crises, the frequency of hospital admissions and the transfusion requirements, the long-term administration of HU in adult patients with sickle cell syndromes can improve survival. These results highlight the beneficial effect of HU in SCD and raise the issue of expanding the use of HU in all patients with these conditions. [Display omitted]

Detection and quantification of the parenchymal abnormalities in emphysema using pulmo-CT

We aimed to determine the degree and extent of parenchymal abnormalities on pulmo-CT in patients with emphysema. The study group consisted of 29 patients (18 male, 11 female; mean age 57.9 ± 13). The diagnosis was based on clinical symptoms, pulmonary function tests (PFT) values, and chest CT findings. All of the patients CT scans were obtained during suspended deep inspiration from the apices to the costophrenic angles. The mean lung attenuation (MLD) and parenchymal abnormalities related to emphysema were quantitatively calculated with tables, histograms and graphics at the whole lung. The lung density measurements revealed a mean density of −898.48 ± 51.37 HU in patients with emphysema and −825.1 ± 25.5 HU in control group. In addition, mean percentage of subthreshold attenuation values was found as 12.03 ± 15.75 and 1.07 ± 0.83 in patients with emphysema and control group, respectively. Compared with control group, the patients with emphysema had a significantly lower inspiratory MLD ( p < 0.05). Additionally, statistically significant correlations were seen between the MLD and percentage of subthreshold values ( r = 0.44, p < 0.05). In contrast, there was poor correlation between PFT measurements and the subthreshold values. In conclusion, pulmo-CT is a quick, simple method for quantitative confirmation of the presence of parenchymal abnormalities of lung as mosaic attenuation and should be used in combination with other radiological methods and PFT as it gives additional information to routine examinations in patients with emphysema.

The Medical Research Council PT1 Trial in Essential Thrombocythemia.

Essential thrombocythemia (ET) is associated with arterial and venous thrombosis, hemorrhage and transformation to acute leukemia and myelofibrosis. Cytoreduction with hydroxyurea (Hu) reduces thrombotic risk, but concerns about potential toxicity have led to the widespread use of a newer agent, anagrelide (Ag) as first-line therapy. However, no randomized trials comparing the efficacy and safety of Ag with Hu have been performed.The MRC PT1 trial is an international, multi-centre, randomized controlled trial comparing Ag with Hu in patients with ET at high-risk of vascular events (based on age, platelet count or cardiovascular risk factors). The trial was independently conceived, conducted and analysed by the investigators on behalf of the UK Myeloproliferative Disorders Study Group and the MRC Adult Leukaemia Working Party. Patients (newly diagnosed or previously treated) were randomized to receive either Ag plus aspirin (Ag+asp) or Hu+asp. Clinical end-points together with blood and bone marrow morphology were assessed centrally by experts blinded to treatment allocation. With 809 patients randomized and median follow-up of 39 months, it is the largest and most comprehensive randomized study of ET performed to date.Patients in the Ag+asp arm were significantly more likely to reach the primary end-point and several secondary end-points. Intention-to-treat log-rank analyses of time to event indicate that Ag+asp patients were significantly more likely than Hu+asp patients to reach the composite primary end-point of arterial thrombosis, venous thrombosis or major hemorrhage (55 v 36 events; odds ratio 1.57; 95% CI 1.04–2.37; p=0.03). Ag+asp was also associated with increased rates of arterial thrombosis (37 v 17 events; OR 2.16; 95% CI 1.27–3.69; p=0.004) and major hemorrhage (22 v 8 events; OR 2.61; CI 1.27–5.33; p=0.008) but, interestingly, decreased venous thrombosis compared to Hu+asp (3 v 14 events; OR 0.27; CI 0.11–0.71; p=0.006). Myelofibrotic transformation, the diagnosis of which required new clinical and/or laboratory features in addition to grade III/IV reticulin fibrosis, was significantly increased in the Ag+asp arm (16 v 5 events; OR 2.92, CI 1.24–6.86, p=0.01). Transformation to MDS/AML was comparable between the two arms (4 Ag+asp v 6 Hu+asp), although the small number of transformations and short follow-up prevent firm conclusions about leukemogenicity. Overall survival was not statistically different. Ag+asp was more poorly tolerated than Hu+asp. In the Ag+asp arm significantly fewer patients remained on their allocated treatment (p<0.00001) and there were significantly greater rates of cardiovascular (p<0.0001), gastrointestinal (p=0.02), neurological (p<0.0001) and constitutional (p<0.001) side effects. Long-term control of the platelet count was comparable between the two arms.These results demonstrate that, compared to Hu+asp, Ag+asp is associated with an excess rate of arterial thrombosis, major hemorrhage and myelofibrotic transformation but decreased venous thrombosis, and suggest that Hu should remain first-line therapy in patients with ET at high risk for vascular events.

Thin-section CT findings in flock worker's lung, a work-related interstitial lung disease.

To characterize the thin-section computed tomographic (CT) features of flock worker's lung (FWL) and to determine whether these features may be used to distinguish workers with FWL from flock workers who do not fulfill diagnostic criteria for FWL. Thin-section CT images obtained in 43 flock workers (including 11 with FWL) were reviewed independently by radiologists blinded to occupational and clinical details. CT features recorded included ground-glass opacities, consolidation, micronodules, reticular abnormality, and septal thickening. Thirty-five of the CT scans (including nine obtained in patients with FWL) were also studied by using quantitative image analysis. The Student t test was used to compare mean lung attenuation between the workers with FWL and those without it. Every patient with FWL and 19 (59%) of the 32 exposed flock workers who did not meet criteria for the disease had an abnormal thin-section CT scan. The most common findings in FWL were ground-glass opacities and micronodules. Quantitative analysis showed a mean lung attenuation of -736.4 HU in patients with FWL, compared with -775.0 HU in workers without the disease (P <.05). While ground-glass opacities, micronodules, or both were found in all cases of FWL, these abnormalities were also present in a substantial proportion of symptomatic flock workers who did not satisfy current criteria for FWL. Although nonspecific, these findings should suggest the diagnosis of FWL in exposed individuals.