European Radiology

, Volume 13, Issue 9, pp 2212–2221

Long-term sequelae of Farmer's lung disease in HRCT: a 14-year follow-up study of 88 patients and 83 matched control farmers

Authors

    • Department of Clinical RadiologyKuopio University Hospital
  • R. A. Erkinjuntti-Pekkanen
    • Department of Pulmonary DiseasesKuopio University Hospital
  • P. L. K. Partanen
    • Department of Clinical RadiologyKuopio University Hospital
  • H. T. Rytkönen
    • Department of Clinical RadiologyKuopio University Hospital
  • R. L. Vanninen
    • Department of Clinical RadiologyKuopio University Hospital
Chest

DOI: 10.1007/s00330-003-1848-1

Cite this article as:
Malinen, A.P., Erkinjuntti-Pekkanen, R.A., Partanen, P.L.K. et al. Eur Radiol (2003) 13: 2212. doi:10.1007/s00330-003-1848-1

Abstract.

The aim of this study was to compare high-resolution computed tomography (HRCT) findings of long-term farmer's lung (FL) patients and control farmers. We studied 88 FL patients and 83 matched control farmers with a mean follow-up time of 14 years. Emphysematous, fibrotic, and miliary changes were recorded by HRCT. The pattern of emphysema and location and distribution of other findings were evaluated in detail. Emphysema was found in 20 (23%) FL patients and in 6 (7%) controls (p=0.005). Recurrences of FL attacks increased (p=0.021) the risk of emphysema. Prevalence of fibrosis (17 vs 10%, p=0.16) and miliary changes (11 vs 4%, p=0.06) did not differ significantly in patients and controls. Among FL patients, emphysematous, fibrous, and miliary changes were more pronounced at the base than in the upper parts of the lung (p<0.02). In slice analysis, the pattern of emphysema was more polymorphous (p=0.001) and the distribution of fibrotic and miliary changes was more variable among FL patients than controls. Emphysema in HRCT is more common in FL patients than matched control farmers, and the occurrence is increased by recurrences of FL. Emphysematous, fibrous, and miliary changes in FL patients HRCT are multiform and predominate in the lower parts of the lung.

Keywords

Computed tomographyFarmer's lungSequelaeEmphysemaFibrosis

Introduction

Farmer's lung disease (FL), a form of hypersensitivity pneumonitis (HP; also called allergic alveolitis) caused by repeated inhalation of mouldy material, is still an important occupational disease among farmers in some countries [1, 2]. Since it involves respiratory bronchioles and alveoli, the term "bronchioloalveolitis" has been suggested for it [3].

Clinically, FL is divided into three stages—acute, subacute, and chronic [4]—each with different symptoms and radiological findings. On the basis of previous follow-up studies, impaired diffusing capacity (DLCO) and airway obstruction seem to be the most common clinical sequelae of FL [5, 6]. As these findings are commonly seen in emphysema, they suggest that emphysema may be an important long-term morphological and radiological sequelae of FL; however, long-term high-resolution computed tomography (HRCT) sequelae of FL have seldom been reported.

Previous studies of radiological findings in FL were based on chest X-rays [7, 8, 9], which showed miliary changes and nodular shadowing in the acute stage and mainly fibrosis in the chronic stage; however, conventional chest radiography is not very accurate in detecting minor lung parenchymal changes, especially emphysema [10, 11, 12]. Although the CT findings of HP of different causes and the distribution of findings have been described by several authors [6, 11, 13, 14, 15, 16, 17, 18, 19, 20], the study groups involved have been quite small. In addition, smoking habits have not always been registered, whereas disease stage, number of recurrences, and follow-up time are often unclear. Another limitation in previous studies is that control groups have seldom been used.

Several studies have shown that farming itself is a risk factor for respiratory disorders [21, 22, 23]: a study in Finnish farmers found a 40% excess mortality rate from respiratory causes, for example [24]; however, studies on the frequency of morphological changes in the lung parenchyma associated with farming itself and their HRCT characteristics are scanty. The effect of farming itself should, however, always be taken into account when evaluating the surplus changes caused by FL.

The present study was designed to systematically evaluate the long-term sequelae in FL patients' lung parenchyma by HRCT, comparing these farmers with matched control farmers.

Materials and methods

Study population

Altogether 88 consecutive patients, initially diagnosed to suffer their first acute attack of FL in our university hospital [25], underwent a long-term follow-up HRCT examination after a mean follow-up time of 14 years (range 11–16 years). Eighty-three other farmers, matched with the FL patients according to age, gender, smoking habits, and main farming operation, formed the control group for HRCT examination. The control farmers were selected from the 2424 farmers who participated in the "Farmers' Work and Health 1979" survey [26]. None of the accepted control farmers had had diagnosed FL disease. All FL patients and control farmers had reported cattle tending as their main farm operation. The basic characteristics of the study population are shown in Table 1. The detailed clinical information of the study population has been described previously [27].
Table 1.

Basic characteristics of the study population. FL farmer's lung

 

FL patients

Control farmers

n (%)

Mean (range)

n (%)

Mean (range)

Total

88 (51)

 

83 (49)

 

Women

68 (77)

 

64 (77)

 

Men

20 (21)

 

19 (21)

 

Age (years)

 

60 (38–76)

 

60 (40–76)

Non-smokers

71 (81)

 

68 (82)

 

Smokers

17 (19)

 

15 (18)

 

Ex-smokers smoking years

13

21 (12–33)

7

24 (15–35)

Current smokers smoking years

4

26 (18–35)

8

24 (15–50)

Current farmers

38 (43)

 

37 (45)

 

Ex-farmers

50 (57)

 

46 (55)

 

At the time of the HRCT examination none of the FL patients had acute FL. One FL patient had had the last recurrence 8 months before the radiological examination. In all other patients the interval was more than 2 years. Of the FL patients, 66% had had only one FL attack, 22% had a history of one recurrence, 7% had two, and 2% had three recurrences.

This study was approved by the ethics committee of the university of our district and city university hospital.

The HRCT examination was carried out with a Siemens Somatom Plus-S scanner (Siemens, Erlangen, Germany). Imaging was performed with the subject in the supine position and at end-inspiratory state. One-millimeter-thick slices at 20-mm intervals (137 kVp, 275 mA, 1-s scanning time) were obtained from the diaphragm to the lung apex, seven to ten in total. A high-frequency reconstruction algorithm was used and the zoom factor was as large as possible. Scans were filmed in 12-in-1 format with a window setting of 1200/−500 Hounsfield units (HU).

The presence of low-attenuation areas was interpreted to represent emphysema according to criteria described by Sanders et al [28], in which emphysematous changes are decreased attenuation, few or no vessels, and bullae with a well- or ill-defined wall. The scale was: 0=normal; 1=emphysema in <25% of the slice; 2=emphysema in 25–50% of the slice; 3=emphysema in 50–75% of the slice; and 4=emphysema in >75% of the slice. The maximum possible score of ten slices was therefore 40. Emphysema related to fibrosis or scarring was not regarded as emphysema.

The fibrotic and miliary changes by HRCT were graded according to a modified Hapke's classification [7] in which 0=normal, 1=minimal changes, 2=definite changes, and 3=marked changes. For fibrotic changes score 1=reticular and diffuse, fine, linear or peripheral, ill-defined, nodular opacities of varying size; 2=coarse linear opacities, radiating from the hila, perhaps with slight contraction of one lobe; and 3=coarse linear opacities, small cyst formation, and deformity due to contractions of lung. For miliary changes, the score system was 1=abnormalities so slight that they would be passed as within normal limits by a clinician or radiologist nor alerted by the clinical history to the possibility of farmer's lung; 2=definite change—discrete, sharply defined, punctiform, or so fine as to be ground glass in appearance; and 3=changes similar to those listed in score 2 with additional poorly defined "soft" opacities which become confluent in places.

The HRCTs were analyzed by two experienced radiologists who were blinded to the clinical data. The final results were based on a consensus reading of these two radiologist (K.P. and H.R.). Concordance of interpretation has been published previously [29]. A third radiologist (A.M.), who was also blinded to the clinical data and the results of the other findings, reread all HRCT examinations for emphysematous changes. Intra- and interobserver reproducibility proved to be good [30]. In addition, after a 1-year interval the third radiologist (A.M.) classified the pattern of emphysema and distribution of fibrotic and miliary changes and recorded changes of micronodules and mosaic pattern of parenchyma to obtain more detailed information about the miliary changes. The results of a consensus reading were available. The micronodules were defined as discrete, small, or focal round opacity with a diameter of no more than 7 mm [31]. The mosaic pattern was recorded if regional differences in lung attenuation in parenchyma were seen, and vessels in the lucent regions of lung appeared smaller than in denser lung regions [32]. The pattern of emphysema was classified as centrilobular, paraseptal, or bullae according to Austin et al. [31]. Emphysema was classified as multiform when two patterns of emphysema were seen in the same slice. The location of emphysema among the ten slices and distribution of all other findings within each slice were analyzed slice by slice. The distribution of fibrosis and miliary changes within each slice was classified as peripheral/central, and dorsal/ventral. Findings were considered widespread if they were found in all four distributions. The location of changes were defined as lower and upper part of the lung with respect to the level of carina.

Statistical analysis

For statistical analysis, the total emphysema, fibrosis, and miliary scores of each patient were characterized into the following two groups: a score of ≥5 represented pathological HRCT, and scores 0–4 represented normal HRCT. This is the classification used in producing the results herein, unless otherwise specified. Ten slices were obtained from the majority (134 of 171, 78%) of the subjects, but only nine slices were obtained from 27 subjects and eight slices from nine subjects and seven slices from one subject due to smaller thorax. Thirteen of these 37 subjects had definite changes; the rest had only minor changes, so cutoff point of five for definite changes was also used for these subjects. Fisher's Exact test or the chi-square test was used for group comparisons. In order to evaluate the associations between the severity of emphysematous, fibrotic, and miliary changes, the scores of each patient were divided into four groups: score 0 as normal; 1–4 as mild; 5–9 as moderate; and ≥10 as severe. The Spearman correlation coefficient was used to test concurrent occurrence of different findings. Normality of all continuous variables was tested with Kolmogorov-Smirnov one-sample test. Since the distribution of the variables clearly deviated from the normal distribution, Mann-Whitney test was used to analyze the effect of recurrent FL attacks with the severity of emphysematous, fibrous, and miliary changes. The non-smoking study subjects were also analyzed separately, and statistically significant results of the non-smoking subjects are reported separately.

Results

Prevalence and severity of findings

The prevalence of definite (score ≥5) emphysematous, fibrous, and miliary findings are shown in Table 2. Significantly more of the control farmers (51 of 83, 61%) than FL patients (40 of 88, 45%) had completely normal HRCT (score for emphysema, fibrosis, and miliary changes=0; p=0.036). Emphysema as the sole abnormality in HRCT was seen in 12 (14%) FL patients but only in 4 (5%) control farmers, whereas sole fibrosis was seen in 5 (6%) FL patients and in 5 (7%) controls. Miliary changes alone were seen in 5 (6%) patients but only in 2 (2%) controls. All detected miliary changes were ground-glass opacity, whereas mosaic perfusion was not seen. Concurrent occurrence of different definite HRCT parenchymal findings was seen in 11 (13%) FL patients. Only 1 control farmer had micronodules with moderate fibrous changes; otherwise, micronodules were not observed. The current smokers and ex-smokers did not differ statistically significantly when the amount of emphysematous, fibrous, or miliary changes was evaluated, so the ex- and current smokers were combined as smokers in the statistical analysis.
Table 2.

Prevalence of high-resolution CT findings among FL patients and control farmers

 

FL patients

Control farmers

Significance (p)

All (n=88)

Non-smoking (n=71)

All (n=83)

Non-smoking (n=68)

All

Non-smoking

Definite emphysema

20

13

6

3

0.005

0.010

Definite fibrosis

15

12

8

8

0.156

0.388

Definite miliary

10

9

3

3

0.056

0.083

No definite changes

55

46

69

57

0.003

0.010

Total score ≥5 was considered to indicate definite emphysematous, fibrous, and miliary changes

The p-value indicates statistical significance between the FL and control groups

The severity of changes in the slice analysis of the study subjects with definite findings are shown in Table 3. The severity of emphysema in the FL patients differed statistically significantly from that in the control farmers, as they had more slices with mild emphysema than did control farmers.
Table 3.

Severity scores of the different findings in a slice of those FL patients and control farmers with definite (total score ≥5) emphysematous, fibrous, or miliary changes

Score

Emphysemaa

Fibrosisb

Miliaryc

Patient slices

Control slices

Patient slices

Control slices

Patient slices

Control slices

0

59 (30)

7 (12)

50 (34)

25 (34)

14 (15)

4 (15)

1

103 (52)

22 (39)

50 (34)

27 (37)

44 (46)

16 (59)

2

35 (18)

17 (30)

34 (24)

21 (28)

37 (38)

7 (26)

3

0 (0)

11 (19)

12 (8)

1 (1)

1 (1)

0 (0)

Total no. of slices

197

57

146

74

96

27

Numbers in parentheses are percentages

The p-value indicates statistical significance between the FL and control groups. Emphysema score 4 was not found

ap<0.001

bp=0.201

cp=0.579

There was a significant correlation between the four-class grades of severity of emphysema and fibrosis (r=0.32, p=0.002) in the FL patients which remained statistically significant among the non-smoking FL patients as well (r=0.30, p=0.02; Fig. 1). Among FL patients, no correlation was observed between the severity of fibrotic and miliary changes or emphysema and miliary changes. The controls showed a significant correlation between the severity of emphysema and miliary changes (r=0.29, p=0.009) and severity of fibrotic and miliary changes (r=0.22, p=0.04). Fifty-eight (66%) FL patients had had a single FL attack, 22 (25%) had had one recurrence of FL, 6 (7%) patients had had two, and 2 (2%) patients had had three recurrences. The effects of the FL recurrences on the HRCT findings are shown in Table 4. For non-smoking FL patients p-value for emphysema was 0.010; otherwise, the effect of recurrences on fibrosis and miliary changes was not statistically significant.
https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1fhb1a-b.jpg
Fig. 1a, b.

A 65-year-old non-smoking Farmer's lung (FL) patient (first FL attack 16 years ago and one recurrence 8 months previously). a The upper part of the lung has remained normal, but b the lower parts of the lung show fibrous (small arrows) and emphysematous (large arrows) changes. The total emphysema score was 8 (moderate) and fibrous score 8 (moderate)

Table 4.

Effect of recurrences of FL attacks on emphysematous, fibrous, and miliary changes. Groups were congruent according to age and smoking habits

 

One FL attack (n=58)

Two or more attacks (n=30)

Significance (p)

Non-smokers (n)

47

24

1.000

Age (years)

60.3 (±8.9)

59.4 (±8.5)

0.459

Emphysema score

1.4 (±3.1)

3.6 (±5.2)

0.021

Fibrosis score

1.8 (±3.3)

3.4 (±6.4)

0.164

Miliary score

1.4 (±4.1)

1.6 (±4.3)

0.732

Values are mean±SD

Pattern and location of emphysema

When HRCT examination was analyzed slice by slice, more FL patients than controls had multiform emphysema (p=0.001). All FL patients with definite emphysema (n=20) on HRCT had centrilobular emphysema. In the FL group, 8 patients (40%) had pure centrilobular emphysema, 5 (25%) had both centrilobular, paraseptal, and bullous emphysema together, 3 patients (15%) had centrilobular emphysema with bullae, and 4 (20%) had centrilobular emphysema with paraseptal changes (Fig. 2). The size of the bullae was between 1 and 2 cm. Also among the smoking FL patients, centrilobular and paraseptal emphysema was a more common finding than bullous type of emphysema, which was seen only in 1 patient. Four control farmers had pure centrilobular emphysema and two had centrilobular emphysema associated with paraseptal emphysema.
https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1fhb2a-d.jpg
Fig. 2a–d.

High-resolution CT of FL patients with different patterns of emphysema (a centrilobular, b bullae, c, paraseptal, d cicatrix). Cicatrix air-space enlargements are not considered as emphysema. Emphysematous areas are indicated with arrows

When the slices were divided into two groups at the level of the carina, the 20 FL patients with definite emphysema (score ≥5) had emphysematous slices (some of scores 1–4) more often found below the carina (88% of slices) than above it (53% of slices; p≤0.001). In the control farmers the corresponding values were 100% below the carina and 75% above the carina (p=0.004), respectively. This finding remained significant among the non-smoking subjects. Centrilobular and bullous emphysema predominated at the base of the lung, whereas paraseptal emphysema was evenly distributed. The severity of emphysema was more evenly distributed in the control farmers than in the FL patients. Figure 3 shows the location and the mean severity scores of emphysema in FL patients and controls with definite emphysema.
https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1flb3a-b.gif
Fig. 3. a

Mean emphysema scores (range 0–4) in HRCT slices of the FL patients with definite emphysema (score ≥5, n=20, total number of slices=197). b Control farmers with definite emphysema (score ≥5, n=6, total number of slices=57). The FL patients have more emphysema at the lower parts of the lungs, whereas in control farmers the scores are more evenly distributed

Location and distribution of fibrosis and miliary changes

The location and the mean severity scores of the slices of all FL patients and controls with fibrosis and miliary changes (score ≥5) are shown in Figs. 4 and 5. In the 15 FL patients with definite fibrosis (score ≥5, n=146 slices) the fibrotic slices were more often located at the lower parts than at the upper parts of the lung (p <0.001). In the 10 FL patients with definite miliary changes (score ≥5, n= 96 slices) the miliary slices showed a similar tendency to be located at the lower part of the lung (p=0.021). In the 8 control farmers with definite fibrosis (n=74 slices) and 3 with miliary changes (n=27 slices) fibrotic and miliary changes were evenly distributed (p=0.085 and p=0.596, respectively).
https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1flb4a-b.gif
Fig. 4.

Mean fibrosis scores (range 0–3) in HRCT slices of the FL patients with definite fibrosis (score ≥5, n=15, total number of slices=146). b Control farmers with definite fibrosis (score ≥5, n=8, total number of slices=74). The FL patients have more fibrosis at the lower parts of the lungs, whereas in control farmers the scores are more evenly distributed

https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1flb5a-b.gif
Fig. 5.

Mean of miliary scores (range 0–3) in HRCT slices of the FL patients (n=10, total number of slices=96), and b control farmers (n=3, total number of slices=27) with definite miliary changes (score ≥5). The FL patients' miliary changes tend to be located at the lower part of the lungs. The control farmers also had more severe miliary changes at the lower parts of the lungs

The distribution of fibrosis within each slice was classified as peripheral and/or central, dorsal and/or ventral. If the changes were found in all four distributions of the lung slice, fibrosis was classified as widespread. Widespread fibrosis was more often found in the control farmers (47% of the slices with fibrosis) than in the FL patients ( 29% of the slices with fibrosis; p=0.048; Fig. 6). The most common distribution of fibrosis among the FL patients was purely peripheral, both ventrally and dorsally, distributed fibrosis (56% of slices with fibrosis). Among controls, this type of distribution of fibrosis was seen in 51% of the slices (p=0.143). Fibrosis extending to central areas of the slice, but not widespread, was found in 15% of the slices with fibrosis of FL patients but in only 2% of slices of controls (p=0.016). Detailed information on the distribution of fibrosis within the HRCT slices is shown in Fig. 7. In general, FL patients had more variably distributed fibrosis than controls.
https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1fhb6.jpg
Fig. 6.

A 48-year-old non-smoking woman who has had three recurrences of FL, the most recent 5 years previously. The HRCT shows widespread fibrosis associated with areas of emphysema (arrows)

https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1fmb7.gif
Fig. 7.

The distribution of fibrous changes (black area indicates location of abnormal findings) within each axial half slice in subjects with definite fibrosis (score ≥5; FL patients: n=15, 96 slices; controls: n=8, 49 slices with fibrosis)

The distribution of miliary changes within each slice was correspondingly classified. Pure centrally located miliary changes were detected more often in FL patients' slices (39% of the slices with miliary changes) than in controls' slices (13%; p=0.002). The distribution of miliary changes was more often widespread in controls (in 83% of the slices) than in FL patients (in 52% of the slices; p=0.009). Detailed results are shown in Fig. 8.
https://static-content.springer.com/image/art%3A10.1007%2Fs00330-003-1848-1/MediaObjects/s00330-003-1848-1fmb8.gif
Fig. 8.

Distribution of miliary changes (black area indicates location of abnormal findings) within each axial half slice in subjects with definite miliary changes (score ≥5; FL patients: n=10, 82 slices; controls: n=3, 23 slices)

Discussion

The majority of FL patients (63%) had no abnormal parenchymal findings at HRCT; however, as a long-term sequelae, significantly more FL patients than control farmers had mild but polymorphous emphysema spearing the upper parts of the lung. The recurrences of FL attacks significantly increased the risk of emphysema. The FL patients and control farmers did not significantly differ with regard to amount of fibrosis and miliary changes, but the location and distribution of the changes differed significantly. Among FL patients these changes were located at the lower parts of the lung and they had significantly more often fibrosis and miliary changes distributed centrally than control farmers. Severity of emphysema and fibrosis was correlated in FL patients even when cicatrix emphysematous changes were excluded. The reported long-term sequelae of FL patients varies, partly because of selection bias and partly because of the limitations of the imaging methods used [6, 11, 13, 16, 19, 20]. Only a few studies [13, 33] report open-lung or transbronchial biopsies of the chronic FL patients, but the results are not reported in detail. Pathological correlation is seldom available as deaths caused by FL are rare [34], and definite pathological diagnosis of emphysema, especially, would require the inflated whole lung or lobe specimen. Several studies have demonstrated fibrotic changes, as evaluated by plain chest radiographs, to be the major radiological long-term sequelae of FL [7, 35]. Detection of emphysema, especially if it is not very pronounced, is more accurate by HRCT than by chest radiograph [12, 28]. In our previous study [29, 36] emphysematous changes on HRCT correlated strongly with pulmonary function defects typical of emphysematous changes (impaired FEV1, FEV%, and DLCO). In that study also fibrosis on HRCT correlated with restrictive pulmonary function tests (pft) and impaired DLCO, but miliary changes on HRCT did not correlate significantly with pft. The HRCT has proved to be superior in showing micronodules and ground-glass opacification [6, 11, 14, 33] in HP patients.

Although some CT studies have reported chronic or long-term changes of HP [11, 13, 14, 16, 17, 33], the patients have been mainly other than FL patients. A thin-section CT study of bird breeder HP [16] suggests that emphysema must be considered as an integral part of bird breeder lung, varying from areas of focal air trapping to diffuse emphysematous changes. Lalancette et al. [6] found emphysema as the main abnormality in HRCT in 7 of 14 chronic and in 2 of 19 of acute FL patients. They concluded that emphysema develops late in the course of FL. A previous study [8] with chest X-rays suggests that repeated exposures may lead to interstitial fibrosis and emphysema. Recently, Cormier et al. [19] reported HRCT characteristics of 95 FL patients. They found that emphysema, as a long-term change, was more frequent than interstitial fibrosis. The results of the present study support those of Lalancette et al. [6] and Cormier et al. [19] that emphysema is the main abnormality to be found, and ground-glass abnormalities as a long-term sequelae of FL are seen in only a minority of the FL patients.

In a previous follow-up study of FL [37], symptomatic recurrences, especially five or more, correlated with impaired pulmonary functions and radiological abnormalities. Especially in chronic pigeon breeders lung fibrosis seems to increase even if exposition has ceased [38]. In the present study, one or more recurrences were associated with the risk of emphysema but not with the risk of fibrosis.

Ground-glass opacities have been reported to be the most common finding among acute and subacute FL patients' thin-section CT, but these abnormalities seem to diminish among the FL patients who have avoided environmental contact with antigen and are in clinical remission [17, 19]. Remy-Jardin et al. [16] suggest that ground-glass attenuation might reflect reversible interstitial lung changes that characterize HP, and further that the concurrent presence of ground-glass attenuation and/or micronodules with honeycombing on CT scans strongly suggests subacute changes superimposed on chronic disease. Hapke et al. [7] previously noticed that micronodules persisting for more than 1 year should be looked upon as chronic type changes. Another study [39] suggests that the changes are fibrous, if ground-glass opacities are associated with other fibrous changes. It seems that ground-glass opacities seen at HRCT of FL patients might reflect subacute disease superimposed on the chronic changes if exposure is continuing, or fibrosis, if exposure has ceased, especially if the changes are permanent.

The distribution of changes of HP have been reported, but the results have varied, mainly as a result of the different stage (acute, subacute, chronic) of disease and/or paucity of patients [9, 11, 13, 14, 16, 17, 33]. The distribution of long-term sequelae, especially in FL disease, have seldom been reported. Both lower-zone predominance [11, 17] and middle-zone predominance [13] of fibrosis have been reported. Relatively spared lung bases and apex are regularly reported. A study of 45 subacute and chronic FL patients [16] reported linear attenuation limited to the lower-lung zones, whereas emphysematous changes were diffusely distributed. Another study of 95 acute and chronic FL patients [19] reported that ground-glass changes predominated in the lower lobes of the lungs, whereas other abnormalities had no preferential distribution. In the present study emphysematous, fibrous, and miliary changes as the long-term finding of the FL patients' HRCT predominated in the lower parts of the lungs. Even though the most typical distribution of fibrosis was purely peripheral, centrally distributed fibrosis was also seen in FL patients, but not in controls. Only 2 patients had advanced fibrosis at the lower parts of the lungs, but no honeycombing was seen as in idiopathic pulmonary fibrosis.

An important strength of the present study is that the control group was carefully and statistically relevantly selected. In addition, all FL patients of the present study were at the chronic stage of the disease, constituting a uniform population whose precise follow-up time is recorded. The limitations of the present study were associated with the HRCT classification methods. Firstly, Hapke's classification is established for chest radiographs, not for CT. The HRCT is known to reveal more detailed information, especially of nodules and ground-glass opacification [11, 14]; however, we evaluated the films also for mosaic perfusion and micronodules, even if Hapke's classification does not separate them. Another possible drawback may be the fact that the right and left lungs were not viewed separately; however, FL or HP diseases have been reported to be bilateral, symmetrical diseases [16, 33]. Some control farmers had more severe emphysema than FL patients. This might be explained by a selection bias; as the symptomatic control farmers were more willing to participate in research than the healthy farmers.

Bronchiolitis, which is seen in subacute FL, causes air trapping. In the future there is a need to distinguish air trapping from emphysema in thin-section CT, if it is possible. Repeated HRCT inspiratory and expiratory examinations, and pulmonary function tests, including plethysmography, may give further insight into this question.

Conclusion

In conclusion, in the majority of FL patients long-term HRCT findings remain normal. More FL patients than a matched control population have emphysema, and in addition, recurrences of FL significantly increase the risk of emphysema. The emphysematous, fibrous, and miliary changes in the cattle-tending FL patients are typically located at the lower parts of the lung, and the distribution of changes and the pattern of emphysema are different from those in matched control farmers.

Acknowledgements. This work was supported in part by grants given to A. Malinen from The Finnish Anti-Tuberculosis Association Foundation, Pehr Oscar Klingendahl Foundation, and EVO Funding grant.

Copyright information

© Springer-Verlag 2003